HNF gene transcriptions

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Editor-In-Chief: Henry A. Hoff

Hepatic nuclear factors (HNFs) bind through their DNA-binding domain (DBD) to consensus elements (A/G/T)(A/T)(A/G)T(C/T)(A/C/G)AT(A/C/G/T)(A/G/T), resulting in gene transcription.[1]

HNF1s

Gene ID: 6927 is HNF1A HNF1 homeobox A aka TCF1 on 12q24.31: "The protein encoded by this gene is a transcription factor required for the expression of several liver-specific genes. The encoded protein functions as a homodimer and binds to the inverted palindrome 5'-GTTAATNATTAAC-3'. Defects in this gene are a cause of maturity onset diabetes of the young type 3 (MODY3) and also can result in the appearance of hepatic adenomas. Alternative splicing results in multiple transcript variants encoding different isoforms."[2]

  1. NP_000536.6 hepatocyte nuclear factor 1-alpha isoform 2 [variant 2].[2]
  2. NP_001293108.2 hepatocyte nuclear factor 1-alpha isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."[2]

Gene ID: 6928 is HNF1B HNF1 homeobox B aka HNF2, TCF2, on 17q12: "This gene encodes a member of the homeodomain-containing superfamily of transcription factors. The protein binds to DNA as either a homodimer, or a heterodimer with the related protein hepatocyte nuclear factor 1-alpha. The gene has been shown to function in nephron development, and regulates development of the embryonic pancreas. Mutations in this gene result in renal cysts and diabetes syndrome and noninsulin-dependent diabetes mellitus, and expression of this gene is altered in some types of cancer. Multiple transcript variants encoding different isoforms have been found for this gene."[3]

  1. NP_000449.1 hepatocyte nuclear factor 1-beta isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."[3]
  2. NP_001159395.1 hepatocyte nuclear factor 1-beta isoform 2: "Transcript Variant: This variant (2) uses an alternate in-frame splice site in the central coding region, compared to variant 1. The resulting isoform (2) lacks an internal segment, compared to isoform 1."[3]
  3. NP_001291215.1 hepatocyte nuclear factor 1-beta isoform 3: "Transcript Variant: This variant (3) differs in the 3' UTR, uses an alternate in-frame splice site in the central coding region, and lacks two alternate exons in the 3' coding region, resulting in a frameshift compared to variant 1. The resulting isoform (3) is shorter, and contains a distinct C-terminus, compared to isoform 1."[3]

Gene ID: 79618 is HMBOX1 homeobox containing 1 aka hepatocyte nuclear factor 1 (HNF-1), N terminus (HNF1LA) on 8p21.1-p12.[4]

  1. NP_001129198.1 homeobox-containing protein 1 isoform 1: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2, and 3 all encode the same isoform (1)."[4]
  2. NP_001311311.1 homeobox-containing protein 1 isoform 1: "Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2, and 3 all encode the same isoform (1)."[4]
  3. NP_001311312.1 homeobox-containing protein 1 isoform 2 [variant 4].[4]
  4. NP_001311313.1 homeobox-containing protein 1 isoform 2 [variant 5].[4]
  5. NP_001311314.1 homeobox-containing protein 1 isoform 3 [variant 6].[4]
  6. NP_001311315.1 homeobox-containing protein 1 isoform 4 [variant 7].[4]
  7. NP_001311316.1 homeobox-containing protein 1 isoform 5 [variant 8].[4]
  8. NP_001311317.1 homeobox-containing protein 1 isoform 5 [variant 9].[4]
  9. NP_001311318.1 homeobox-containing protein 1 isoform 6 [variant 10].[4]
  10. NP_001311319.1 homeobox-containing protein 1 isoform 6 [variant 11].[4]
  11. NP_001311320.1 homeobox-containing protein 1 isoform 7 [variant 12].[4]
  12. NP_001311321.1 homeobox-containing protein 1 isoform 7 [variant 13].[4]
  13. NP_001311322.1 homeobox-containing protein 1 isoform 8 [variant 14].[4]
  14. NP_001311323.1 homeobox-containing protein 1 isoform 8 [variant 15].[4]
  15. NP_001311324.1 homeobox-containing protein 1 isoform 9 [variant 16].[4]
  16. NP_001317427.1 homeobox-containing protein 1 isoform 10 [variant 19].[4]
  17. NP_078843.2 homeobox-containing protein 1 isoform 1: "Transcript Variant: This variant (1) encodes isoform 1. Variants 1, 2, and 3 all encode the same isoform (1)."[4]

HNF3s

"Computer analysis of the 2.3 kb rat a1bg promoter fragment revealed [...] one HNF6/HNF3 binding site at [...] −137/−128 [...]."[1]

The "GH-dependent sexually dimorphic expression conveyed by the 2.3 kb a1bg promoter is enhanced by the HNF6/HNF3 site [...]."[1]

"By extending the electrophoresis run and including nuclear extract from hypophysectomized rats, devoid of GH and thereby lacking HNF6 (Lahuna et al. 1997), the two different complexes were clearly visualized. The complex with the lower mobility is most probably due to the binding of HNF3, in analogy with what was shown by Lahuna et al. for the CYP2C12 HNF6 binding site; HNF3 can bind to the site in the absence of HNF6 (Lahuna et al. 1997)."[1]

"Forkhead (FH), also known as a "winged helix". FH is named for the Drosophila fork head protein, a transcription factor which promotes terminal rather than segmental development. This family of transcription factor domains, which bind to B-DNA as monomers, are also found in the Hepatocyte nuclear factor (HNF) proteins, which provide tissue-specific gene regulation. The structure contains 2 flexible loops or "wings" in the C-terminal region, hence the term winged helix."[5]

Gene ID: 2304 is FOXE1 forkhead box E1 on 9q22.33: "This intronless gene encodes a protein that belongs to the forkhead family of transcription factors. Members of this family contain a conserved 100-amino acid DNA-binding 'forkhead' domain. The encoded protein functions as a thyroid transcription factor that plays a role in thyroid morphogenesis. Mutations in this gene are associated with the Bamforth-Lazarus syndrome, and with susceptibility to nonmedullary thyroid cancer-4."[6]

Gene ID: 2305 is FOXM1 forkhead box M1 aka HNF-3 on 12p13.33. "The protein encoded by this gene is a transcriptional activator involved in cell proliferation. The encoded protein is phosphorylated in M phase and regulates the expression of several cell cycle genes, such as cyclin B1 and cyclin D1. Several transcript variants encoding different isoforms have been found for this gene."[7]

  1. NP_001230017.1 forkhead box protein M1 isoform 4: "Transcript Variant: This variant (4) lacks two alternate in-frame exons and uses two alternate in-frame splice junctions compared to variant 1. The resulting isoform (4) has the same N- and C-termini but is shorter compared to isoform 1."[7]
  2. NP_001230018.1 forkhead box protein M1 isoform 5: "Transcript Variant: This variant (5) lacks two alternate in-frame exons and uses an alternate in-frame splice site compared to variant 1. The resulting isoform (5) has the same N- and C-termini but is shorter compared to isoform 1."[7]
  3. NP_068772.2 forkhead box protein M1 isoform 2: "Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1."[7]
  4. NP_973731.1 forkhead box protein M1 isoform 1: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1)."[7]
  5. NP_973732.1 forkhead box protein M1 isoform 3: "Transcript Variant: This variant (3) lacks two alternate in-frame exons compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1."[7]

Gene ID: 3169 is FOXA1 forkhead box A1 aka HNF3A on 14q21.1: "This gene encodes a member of the forkhead class of DNA-binding proteins. These hepatocyte nuclear factors are transcriptional activators for liver-specific transcripts such as albumin and transthyretin, and they also interact with chromatin. Similar family members in mice have roles in the regulation of metabolism and in the differentiation of the pancreas and liver."[8]

Gene ID: 3170 is FOXA2 forkhead box A2 aka HNF3B on 20p11.21. "This gene encodes a member of the forkhead class of DNA-binding proteins. These hepatocyte nuclear factors are transcriptional activators for liver-specific genes such as albumin and transthyretin, and they also interact with chromatin. Similar family members in mice have roles in the regulation of metabolism and in the differentiation of the pancreas and liver. This gene has been linked to sporadic cases of maturity-onset diabetes of the young. Transcript variants encoding different isoforms have been identified for this gene."[9]

  1. NP_068556.2 hepatocyte nuclear factor 3-beta isoform 1: "Transcript Variant: This variant (1) encodes the longer isoform (1)."[9]
  2. NP_710141.1 hepatocyte nuclear factor 3-beta isoform 2: "Transcript Variant: This variant (2) has a different splice pattern at the 5' end compared to transcript variant 1, resulting in translation initiation from a downstream AUG, and a shorter isoform (2) missing 6 aa from the N-terminus compared to isoform 1."[9]

Gene ID: 3171 is FOXA3 forkhead box A3 aka HNF3G on 19q13.32: "This gene encodes a member of the forkhead class of DNA-binding proteins. These hepatocyte nuclear factors are transcriptional activators for liver-specific transcripts such as albumin and transthyretin, and they also interact with chromatin. Similar family members in mice have roles in the regulation of metabolism and in the differentiation of the pancreas and liver. The crystal structure of a similar protein in rat has been resolved."[10]

Gene ID: 27022 is FOXD3 forkhead box D3 aka HNF3/FH transcription factor genesis on 1p31.3: "This gene belongs to the forkhead family of transcription factors which is characterized by a distinct forkhead domain. Mutations in this gene cause autoimmune susceptibility 1."[11]

Gene ID: 94234 is FOXQ1 forkhead box Q1 aka hepatocyte nuclear factor 3 forkhead homolog 1 on 6p25.3: "FOXQ1 is a member of the FOX gene family, which is characterized by a conserved 110-amino acid DNA-binding motif called the forkhead or winged helix domain. FOX genes are involved in embryonic development, cell cycle regulation, tissue-specific gene expression, cell signaling, and tumorigenesis (Bieller et al., 2001 [PubMed 11747606])."[12]

HNF4s

Gene ID: 3172 is HNF4A hepatocyte nuclear factor 4 alpha on 20q13.12: "The protein encoded by this gene is a nuclear transcription factor which binds DNA as a homodimer. The encoded protein controls the expression of several genes, including hepatocyte nuclear factor 1 alpha, a transcription factor which regulates the expression of several hepatic genes. This gene may play a role in development of the liver, kidney, and intestines. Mutations in this gene have been associated with monogenic autosomal dominant non-insulin-dependent diabetes mellitus type I. Alternative splicing of this gene results in multiple transcript variants encoding several different isoforms."[13]

  1. NP_000448.3 hepatocyte nuclear factor 4-alpha isoform 2: "Transcript Variant: This variant (2) encodes the longest isoform (2, also known as HNF4alpha2)."[13]
  2. NP_001025174.1 hepatocyte nuclear factor 4-alpha isoform 4: "Transcript Variant: This variant (4) contains an alternate 5' terminal exon (resulting in translation initiation from an alternate upstream start codon) and uses an alternate in-frame donor splice site in the 3' coding region compared to variant 2. The resulting shorter isoform (4, also known as HNF4alpha7) has a distinct N-terminus and lacks a 10 aa protein segment in the C-terminal region compared to isoform 2."[13]
  3. NP_001025175.1 hepatocyte nuclear factor 4-alpha isoform 6: "Transcript Variant: This variant (6) contains an alternate 5' terminal exon (resulting in translation initiation from an alternate upstream start codon) and differs at the 3' end that causes a frame-shift compared to variant 2. The resulting shorter isoform (6, also known as HNF4alpha9) has distinct N- and C-termini compared to isoform 2."[13]
  4. NP_001245284.1 hepatocyte nuclear factor 4-alpha isoform 7: "Transcript Variant: This variant (7) contains an additional coding exon in the 5' region that results in translation initiation from an alternate downstream start codon compared to variant 2. The resulting shorter isoform (7) has a distinct N-terminus compared to isoform 2."[13]
  5. NP_001274111.1 hepatocyte nuclear factor 4-alpha isoform 8: "Transcript Variant: This variant (8) differs at the 5' end (resulting in translation initiation from an alternate upstream start codon) and uses an alternate in-frame donor splice site in the 3' coding region compared to variant 2. The resulting shorter isoform (8, also known as HNF4alpha10) has a distinct N-terminus and lacks a 10 aa protein segment in the C-terminal region compared to isoform 2."[13]
  6. NP_001274112.1 hepatocyte nuclear factor 4-alpha isoform 9: "Transcript Variant: This variant (9) differs at the 5' end, which results in translation initiation from an alternate upstream start codon compared to variant 2. The resulting shorter isoform (9, also known as HNF4alpha11) has a distinct N-terminus compared to isoform 2."[13]
  7. NP_001274113.1 hepatocyte nuclear factor 4-alpha isoform 10: "Transcript Variant: This variant (10) differs at the 5' end (resulting in translation initiation from an alternate upstream start codon) and at the 3' end (that causes a frame-shift) compared to variant 2. The resulting shorter isoform (10, also known as HNF4alpha12) has distinct N- and C-termini compared to isoform 2."[13]
  8. NP_787110.2 hepatocyte nuclear factor 4-alpha isoform 5: "Transcript Variant: This variant (5) contains an alternate 5' terminal exon, which results in translation initiation from an alternate upstream start codon compared to variant 2. The resulting shorter isoform (5, also known as HNF4alpha8) has a distinct N-terminus compared to isoform 2."[13]
  9. NP_849180.1 hepatocyte nuclear factor 4-alpha isoform 1: "Transcript Variant: This variant (1) uses an alternate in-frame donor splice site in the 3' coding region compared to variant 2. The resulting shorter isoform (1, also known as HNF4alpha1) lacks a 10 aa protein segment compared to isoform 2."[13]
  10. NP_849181.1 hepatocyte nuclear factor 4-alpha isoform 3: "Transcript Variant: This variant (3) has a different 3' end that causes a frame-shift compared to variant 2. The resulting shorter isoform (3, also known as HNF4alpha3) has a distinct C-terminus compared to isoform 2."[13]

Gene ID: 3174 is HNF4G hepatocyte nuclear factor 4 gamma on 8q21.13.[14]

  1. NP_001317490.1 hepatocyte nuclear factor 4-gamma isoform 2 [variant 2].[14]
  2. NP_004124.5 hepatocyte nuclear factor 4-gamma isoform 1 [variant 1].[14]

"NF1 factors have also been shown to interact directly with the basal transcription machinery as well as with other transcription factors, including Stat5 (Kim & Roeder 1994, Mukhopadhyay et al. 2001) and synergistic effects with HNF4 have been reported (Ulvila et al. 2004). In addition to the HNF6, Stat5 and NF1/Oct sites, the a1bg promoter harbours an imperfect HNF4 site at −51/−39 with two mismatches compared with the HNF4 consensus site. HNF4 is clearly important for the expression of CYP2C12 (Sasaki et al. 1999), however, the −51/−39 region in a1bg was not protected in the footprinting analysis and was therefore not analysed further."[1]

HNF6s

File:Liver expression of a1bg-luciferase constructs.jpg
Liver expression of a1bg-luciferase constructs is diagrammed. Credit: Cissi Gardmo and Agneta Mode.{{fairuse}}

Both "the 2.3 kb and the 160 bp proximal parts of the a1bg promoter direct sex-specific expression of the reporter gene, and that a negative regulatory element resides in the −1 kb to −160 bp region."[1]

The "binding of [...] HNF6 to the respective site by electromobility shift analysis (EMSA) [was verified] using female-derived [rat] liver nuclear extracts. [...] HNF6 bound to the a1bg HNF6 oligonucleotide, but in this case, the mutated oligonucleotide was able to compete for binding when added in large excess [...]. However, [...] the HNF6 binding capacity of the mutated oligonucleotide was clearly reduced. A 20 molar excess of the mutated oligonucleotide had only a marginal effect on the binding of HNF6 [...], whereas a 20 molar excess of unlabelled probe [...] completely abolished binding. Supershift analysis with an HNF6 antibody revealed a complex with a slightly lower mobility than the HNF6 complex [...]. [...] HNF6 could bind to [its] respective site in the a1bg promoter in vitro, and the mutations introduced in respective site abolished binding of the corresponding factor."[1]

The "expression of a −116/−89 deletion construct in which also the HNF6 site was mutated, (−116/−89) delmutHNF6-Luc, [...] the generated luciferase activities were reduced in both sexes [...]. This is in contrast to that mutation/deletion of the sites separately only affected the expression in female livers."[1]

The "−116/−89 region contains a site(s) of importance for the GH-dependent and female-specific expression of the a1bg gene, and that the impact of this region together with the HNF6 site is more complex than mere enhancement of the expression in females."[1]

HNF6 is expressed at higher levels in female than in male rat liver (Lahuna et al. 1997). Indeed, following mutation of the HNF6-binding element, mutHNF6-Luc, the sex-differentiated expression was attenuated due to reduced expression in females. Thus, for a1bg, the sex-related difference in amount of HNF6 is likely to contribute to the sex-differentiated and female characteristic expression."[1]

Nuclear "proteins binding to the a1bg −116/−89 region [are] members of the [nuclear factor 1] NF1 and the [octamer transcription factor] Oct families of transcription factors. NF1 genes are expressed in most adult tissues (Osada et al. 1999). It is not known how NF1 modulates transcriptional activity, and both activation and repression of transcription have been reported (Gronostajski 2000). Cofactors such as [CREB binding protein] CBP/p300 [E1A binding protein p300] and [histone deacetylase] HDAC have been shown to interact with NF1 proteins suggesting modulation of chromatin structure (Chaudhry et al. 1999)."[1]

"Like NF1, Oct proteins have been reported to be involved in activation as well as repression of gene expression (Phillips & Luisi 2000). [...] NF1 and Oct-1 have been shown to, reciprocally, facilitate each other’s binding (O’Connor & Bernard 1995, Belikov et al. 2004)."[1]

In the diagram on the right is liver "expression of a1bg-luciferase constructs. (A) Stat5 and HNF6 consensus sequences and corresponding sites in the 2.3 kb a1bg promoter alongside with the used mutations. (B) Female (black bars) and male (open bars) rats [results]."[1]

GeneID: 3175 ONECUT1 one cut homeobox 1 aka HNF6 on 15q21.3: "This gene encodes a member of the Cut homeobox family of transcription factors. Expression of the encoded protein is enriched in the liver, where it stimulates transcription of liver-expressed genes, and antagonizes glucocorticoid-stimulated gene transcription. This gene may influence a variety of cellular processes including glucose metabolism, cell cycle regulation, and it may also be associated with cancer. Alternative splicing results in multiple transcript variants."[15][1]

HNF6 samplings

For the Basic programs (starting with SuccessablesHNF6.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand in the negative direction (from ZSCAN22 to A1BG) is SuccessablesHNF6--.bas, looking for 3'-(A/G/T)(A/T)(A/G)T(C/T)(A/C/G)AT(A/C/G/T)(A/G/T)-5', 3, 3'-GTGTTAATAA-5', 1725, 3'-TAGTTGATAA-5', 3527, 3'-TTATTAATCG-5', 4229,
  2. negative strand in the positive direction (from ZNF497 to A1BG) is SuccessablesHNF6-+.bas, looking for 3'-(A/G/T)(A/T)(A/G)T(C/T)(A/C/G)AT(A/C/G/T)(A/G/T)-5', 3, 3'-ATGTCCATGG-5', 3581, 3'-TTATTAATCA-5', 4147, 3'-TTATTGATTA-5', 4164,
  3. positive strand in the negative direction is SuccessablesHNF6+-.bas, looking for 3'-(A/G/T)(A/T)(A/G)T(C/T)(A/C/G)AT(A/C/G/T)(A/G/T)-5', 1, 3'-AAATTGATAA-5', 3361,
  4. positive strand in the positive direction is SuccessablesHNF6++.bas, looking for 3'-(A/G/T)(A/T)(A/G)T(C/T)(A/C/G)AT(A/C/G/T)(A/G/T)-5', 1, 3'-GAGTCCATTG-5', 3732,
  5. inverse complement, negative strand, negative direction is SuccessablesHNF6ci--.bas, looking for 3'-(A/C/T)(A/C/G/T)AT(C/G/T)(A/G)A(C/T)(A/T)(A/C/T)-5', 2, 3'-ACATGGACAT-5', 802, 3'-TAATGAACTT-5', 1301,
  6. inverse complement, negative strand, positive direction is SuccessablesHNF6ci-+.bas, looking for 3'-(A/C/T)(A/C/G/T)AT(C/G/T)(A/G)A(C/T)(A/T)(A/C/T)-5', 1, 3'-TTATTGATTA-5', 4164,
  7. inverse complement, positive strand, negative direction is SuccessablesHNF6ci+-.bas, looking for 3'-(A/C/T)(A/C/G/T)AT(C/G/T)(A/G)A(C/T)(A/T)(A/C/T)-5', 3, 3'-AAATTGATAA-5', 3361, 3'-TCATCAACTA-5', 3525, 3'-TTATTAATTC-5', 4542,
  8. inverse complement, positive strand, positive direction is SuccessablesHNF6ci++.bas, looking for 3'-(A/C/T)(A/C/G/T)AT(C/G/T)(A/G)A(C/T)(A/T)(A/C/T)-5', 2, 3'-CCATTGACTC-5', 3736, 3'-ATATTAACAA-5', 4172,

HNF6 UTRs

  1. Negative strand, negative direction: TTATTAATTC at 4542, TTATTAATCG at 4229, TAGTTGATAA at 3527, TCATCAACTA at 3525.
  2. Positive strand, negative direction: AAATTGATAA at 3361.

HNF6 positive direction proximal promoters

  1. Negative strand, positive direction: ATATTAACAA at 4172, TTATTGATTA at 4164, TTATTAATCA at 4147.

HNF6 negative direction distal promoters

  1. Negative strand, negative direction: GTGTTAATAA at 1725, TAATGAACTT at 1301, ACATGGACAT at 802.

HNF6 positive direction distal promoters

  1. Negative strand, positive direction: ATGTCCATGG at 3581.
  2. Positive strand, positive direction: CCATTGACTC at 3736, GAGTCCATTG at 3732.

HNF6 DBD random dataset samplings

  1. HNF6r0: 1, AAATTGATCA at 3572.
  2. HNF6r1: 4, AAGTTGATCT at 4399, GAATTCATGG at 2982, GAATTAATTG at 2902, ATATTCATGG at 2000.
  3. HNF6r2: 9, GTGTCGATTT at 3557, TAATCAATAG at 3453, AAGTCCATTT at 3380, AAGTTGATAG at 3130, GAATTAATAG at 3034, GTATCGATCA at 2361, AAATTAATTG at 1557, GTGTCCATAG at 973, GAATCCATGG at 771.
  4. HNF6r3: 6, TAATTGATCT at 4373, AAATTAATTT at 4349, AAATCCATTT at 4026, AAGTCGATTT at 3688, GAATTAATCA at 1352, AAATTCATTG at 1047.
  5. HNF6r4: 5, AAATTAATGA at 4377, ATATTAATAG at 4167, GTATTAATGA at 2037, GTATTCATGA at 1800, ATATCAATTT at 120.
  6. HNF6r5: 4, ATGTTAATTG at 3567, TTGTCGATGG at 2567, TTGTTGATTA at 892, TTATCCATGG at 654.
  7. HNF6r6: 5, GAGTCAATCG at 4507, AAGTTAATAG at 4444, GTGTCCATTA at 2912, TAATTCATTG at 670, AAGTTCATTG at 147.
  8. HNF6r7: 2, AAATCCATTG at 570, ATGTTGATTT at 110.
  9. HNF6r8: 3, AAGTCAATCT at 4175, AAGTTAATAG at 2665, TTGTTAATGG at 408.
  10. HNF6r9: 2, TAATCGATTG at 3090, GAGTTAATAA at 1493.
  11. HNF6r0ci: 4, TGATGGACAT at 3848, CGATGAACTA at 3231, CAATGGACTT at 1583, TTATTGACTT at 232.
  12. HNF6r1ci: 2, TAATGAATTC at 3089, AAATGGATTA at 1260.
  13. HNF6r2ci: 2, CGATCAACAT at 1754, TGATCGACAT at 271.
  14. HNF6r3ci: 5, AAATTAATTT at 4349, TAATGGACAT at 3885, TGATGGATTT at 3779, AAATTAACTC at 1650, CCATCAACAA at 1309.
  15. HNF6r4ci: 5, TGATCGACTA at 2977, CCATGGACTA at 2055, TTATTGACAT at 1413, AGATTAATTA at 950, ATATCAATTT at 120.
  16. HNF6r5ci: 4, TGATCGATTT at 4468, CCATGAACAC at 3949, AAATTAACAC at 3934, CCATGGACAC at 658.
  17. HNF6r6ci: 4, CCATTAACTA at 2916, ACATGAATAT at 2606, TCATTGATAC at 151, TAATCAACAA at 39.
  18. HNF6r7ci: 5, TGATGGATTA at 4516, TCATTAACTA at 3625, CTATGGATAA at 2720, CTATCAATTA at 1571, AGATGAATAT at 306.
  19. HNF6r8ci: 2, TTATGGATTA at 2090, CAATTAACTT at 610.
  20. HNF6r9ci: 3, CTATGAACAT at 3748, CTATGGACTT at 2866, CGATCAACAA at 2729.

HNF6r arbitrary UTRs

  1. HNF6r0: AAATTGATCA at 3572.
  2. HNF6r2: GTGTCGATTT at 3557, TAATCAATAG at 3453, AAGTCCATTT at 3380, AAGTTGATAG at 3130, GAATTAATAG at 3034.
  3. HNF6r4: AAATTAATGA at 4377, ATATTAATAG at 4167.
  4. HNF6r6: GAGTCAATCG at 4507, AAGTTAATAG at 4444, GTGTCCATTA at 2912.
  5. HNF6r8: 3AAGTCAATCT at 4175.
  6. HNF6r0ci: TGATGGACAT at 3848, CGATGAACTA at 3231.
  7. HNF6r4ci: TGATCGACTA at 2977.
  8. HNF6r6ci: CCATTAACTA at 2916.

HNF6r alternate UTRs

  1. HNF6r1: AAGTTGATCT at 4399, GAATTCATGG at 2982, GAATTAATTG at 2902.
  2. HNF6r3: TAATTGATCT at 4373, AAATTAATTT at 4349, AAATCCATTT at 4026, AAGTCGATTT at 3688.
  3. HNF6r5: ATGTTAATTG at 3567.
  4. HNF6r9: TAATCGATTG at 3090.
  5. HNF6r1ci: TAATGAATTC at 3089.
  6. HNF6r3ci: AAATTAATTT at 4349, TAATGGACAT at 3885, TGATGGATTT at 3779.
  7. HNF6r5ci: TGATCGATTT at 4468, CCATGAACAC at 3949, AAATTAACAC at 3934.
  8. HNF6r7ci: TGATGGATTA at 4516, TCATTAACTA at 3625.
  9. HNF6r9ci: CTATGAACAT at 3748, CTATGGACTT at 2866.

HNF6r arbitrary positive direction core promoters

  1. HNF6r1: AAGTTGATCT at 4399.
  2. HNF6r3: TAATTGATCT at 4373, AAATTAATTT at 4349.
  3. HNF6r3ci: AAATTAATTT at 4349.

HNF6r alternate positive direction core promoters

  1. HNF6r4: AAATTAATGA at 4377.
  2. HNF6r6: AAGTTAATAG at 4444.

HNF6r arbitrary negative direction proximal promoters

  1. HNF6r8: AAGTTAATAG at 2665.
  2. HNF6r6ci: ACATGAATAT at 2606.

HNF6r alternate negative direction proximal promoters

  1. HNF6r7ci: CTATGGATAA at 2720.
  2. HNF6r9ci: CGATCAACAA at 2729.

HNF6r alternate positive direction proximal promoters

  1. HNF6r4: ATATTAATAG at 4167.
  2. HNF6r8: AAGTCAATCT at 4175.

HNF6r arbitrary negative direction distal promoters

  1. HNF6r2: GTATCGATCA at 2361, AAATTAATTG at 1557, GTGTCCATAG at 973, GAATCCATGG at 771.
  2. HNF6r4: GTATTAATGA at 2037, GTATTCATGA at 1800, ATATCAATTT at 120.
  3. HNF6r6: TAATTCATTG at 670, AAGTTCATTG at 147.
  4. HNF6r8: TTGTTAATGG at 408.
  5. HNF6r0ci: CAATGGACTT at 1583, TTATTGACTT at 232.
  6. HNF6r2ci: CGATCAACAT at 1754, TGATCGACAT at 271.
  7. HNF6r4ci: CCATGGACTA at 2055, TTATTGACAT at 1413, AGATTAATTA at 950, ATATCAATTT at 120.
  8. HNF6r6ci: TCATTGATAC at 151, TAATCAACAA at 39.
  9. HNF6r8ci: TTATGGATTA at 2090, CAATTAACTT at 610.

HNF6r alternate negative direction distal promoters

  1. HNF6r1: ATATTCATGG at 2000.
  2. HNF6r3: GAATTAATCA at 1352, AAATTCATTG at 1047.
  3. HNF6r5: TTGTCGATGG at 2567, TTGTTGATTA at 892, TTATCCATGG at 654.
  4. HNF6r7: AAATCCATTG at 570, ATGTTGATTT at 110.
  5. HNF6r9: GAGTTAATAA at 1493.
  6. HNF6r1ci: AAATGGATTA at 1260.
  7. HNF6r3ci: AAATTAACTC at 1650, CCATCAACAA at 1309.
  8. HNF6r5ci: CCATGGACAC at 658.
  9. HNF6r7ci: CTATCAATTA at 1571, AGATGAATAT at 306.

HNF6r arbitrary positive direction distal promoters

  1. HNF6r1: GAATTCATGG at 2982, GAATTAATTG at 2902, ATATTCATGG at 2000.
  2. HNF6r3: AAGTCGATTT at 3688, GAATTAATCA at 1352, AAATTCATTG at 1047.
  3. HNF6r5: ATGTTAATTG at 3567, TTGTCGATGG at 2567, TTGTTGATTA at 892, TTATCCATGG at 654.
  4. HNF6r7: AAATCCATTG at 570, ATGTTGATTT at 110.
  5. HNF6r9: TAATCGATTG at 3090, GAGTTAATAA at 1493.
  6. HNF6r3ci: TAATGGACAT at 3885, TGATGGATTT at 3779, AAATTAACTC at 1650, CCATCAACAA at 1309.
  7. HNF6r5ci: CCATGAACAC at 3949, AAATTAACAC at 3934, CCATGGACAC at 658.
  8. HNF6r7ci: TCATTAACTA at 3625, CTATGGATAA at 2720, CTATCAATTA at 1571, AGATGAATAT at 306.
  9. HNF6r9ci: CTATGAACAT at 3748, CTATGGACTT at 2866, CGATCAACAA at 2729.

HNF6r alternate positive direction distal promoters

  1. HNF6r2: GTGTCGATTT at 3557, TAATCAATAG at 3453, AAGTCCATTT at 3380, AAGTTGATAG at 3130, GAATTAATAG at 3034, GTATCGATCA at 2361, AAATTAATTG at 1557, GTGTCCATAG at 973, GAATCCATGG at 771.
  2. HNF6r4: GTATTAATGA at 2037, GTATTCATGA at 1800, ATATCAATTT at 120.
  3. HNF6r6: GTGTCCATTA at 2912, TAATTCATTG at 670, AAGTTCATTG at 147.
  4. HNF6r8: AAGTTAATAG at 2665, TTGTTAATGG at 408.
  5. HNF6r0ci: CAATGGACTT at 1583, TTATTGACTT at 232.
  6. HNF6r2ci: CGATCAACAT at 1754, TGATCGACAT at 271.
  7. HNF6r4ci: TGATCGACTA at 2977, CCATGGACTA at 2055, TTATTGACAT at 1413, AGATTAATTA at 950, ATATCAATTT at 120.
  8. HNF6r6ci: CCATTAACTA at 2916, ACATGAATAT at 2606, TCATTGATAC at 151, TAATCAACAA at 39.
  9. HNF6r8ci: TTATGGATTA at 2090, CAATTAACTT at 610.

HNF6 analysis and results

Main article: Complex locus A1BG and ZNF497 § HNF6s

Hepatic nuclear factors (HNFs) bind through their DNA-binding domain (DBD) to consensus elements (A/G/T)(A/T)(A/G)T(C/T)(A/C/G)AT(A/C/G/T)(A/G/T), resulting in gene transcription.[1]

Reals or randoms Promoters direction Numbers Strands Occurrences Averages (± 0.1)
Reals UTR negative 5 2 2.5 2.5 ± 1.5 (--4,+-1)
Randoms UTR arbitrary negative 16 10 1.6 1.8
Randoms UTR alternate negative 20 10 2.0 1.8
Reals Core negative 0 2 0 0
Randoms Core arbitrary negative 0 10 0 0
Randoms Core alternate negative 0 10 0 0
Reals Core positive 0 2 0 0
Randoms Core arbitrary positive 4 10 0.4 0.3
Randoms Core alternate positive 2 10 0.2 0.3
Reals Proximal negative 0 2 0 0
Randoms Proximal arbitrary negative 2 10 0.2 0.2
Randoms Proximal alternate negative 2 10 0.2 0.2
Reals Proximal positive 3 2 1.5 1.5 ± 1.5 (-+3,++0)
Randoms Proximal arbitrary positive 0 10 0 0.1
Randoms Proximal alternate positive 2 10 0.2 0.1
Reals Distal negative 3 2 1.5 1.5 ± 1.5 (--3,+-0)
Randoms Distal arbitrary negative 22 10 2.2 1.85
Randoms Distal alternate negative 15 10 1.5 1.85
Reals Distal positive 3 2 1.5 1.5 ± 0.5 (-+1,++2)
Randoms Distal arbitrary positive 28 10 2.8 2.9
Randoms Distal alternate positive 30 10 3.0 2.9

Comparison:

The occurrences of real HNF6 UTRs are outside the randoms, proximals and negative distals are greater than randoms, positive distals are less than randoms. This suggests that the real HNF6s are likely active or activable.

Acknowledgements

The content on this page was first contributed by: Henry A. Hoff.

Initial content for this page in some instances came from Wikiversity.

See also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 Cissi Gardmo and Agneta Mode (1 December 2006). "In vivo transfection of rat liver discloses binding sites conveying GH-dependent and female-specific gene expression". Journal of Molecular Endocrinology. 37 (3\): 433–441. doi:10.1677/jme.1.02116. Retrieved 2017-09-01.
  2. ↑ 2.0 2.1 2.2 RefSeq (April 2015). HNF1A HNF1 homeobox A [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 7 November 2018.
  3. ↑ 3.0 3.1 3.2 3.3 RefSeq (September 2009). HNF1B HNF1 homeobox B [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 8 November 2018.
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 RefSeq (20 April 2020). "HMBOX1 homeobox containing 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2 May 2020.
  5. ↑ S Lu; et al. (17 January 2013). "Conserved Protein Domain Family FH". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 3 May 2020.
  6. ↑ RefSeq (November 2016). "FOXE1 forkhead box E1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2 May 2020.
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 RefSeq (July 2011). FOXM1 forkhead box M1 [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 7 November 2018.
  8. ↑ RefSeq (July 2008). FOXA1 forkhead box A1 [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 7 November 2018.
  9. ↑ 9.0 9.1 9.2 RefSeq (October 2008). FOXA2 forkhead box A2 [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 7 November 2018.
  10. ↑ RefSeq (July 2008). FOXA3 forkhead box A3 [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 8 November 2018.
  11. ↑ RefSeq (November 2008). "FOXD3 forkhead box D3 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2 May 2020.
  12. ↑ OMIM (May 2009). "FOXQ1 forkhead box Q1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 3 May 2020.
  13. ↑ 13.00 13.01 13.02 13.03 13.04 13.05 13.06 13.07 13.08 13.09 13.10 RefSeq (April 2012). "HNF4A hepatocyte nuclear factor 4 alpha [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2 May 2020.
  14. ↑ 14.0 14.1 14.2 RefSeq (29 March 2020). "HNF4G hepatocyte nuclear factor 4 gamma [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2 May 2020.
  15. ↑ RefSeq (December 2012). "ONECUT1 one cut homeobox 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2 May 2020.

External links


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