CArG box gene transcriptions

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Editor-In-Chief: Henry A. Hoff

File:Smooth muscle cell CArG.jpeg
The diagram shows a model for epigenetic regulation of SRF binding to CArG box chromatin. Credit: Oliver G. McDonald, Brian R. Wamhoff, Mark H. Hoofnagle, and Gary K. Owens.

CArG boxes are present in the promoters of smooth muscle cell genes. Template:TOCright

Boxes

A "repeating sequence of nucleotides that forms a transcription or a regulatory signal"[1] is a box.

Consensus sequences

"CArG box [CC(A/T)6GG] DNA [consensus] sequences present within the promoters of SMC genes play a pivotal role in controlling their transcription".[2]

The consensus sequence of CC(A/T)6GG is confirmed.[3]

"MADS-box proteins bind to a consensus sequence, the CArG box, that has the core motif CC(A/T)6GG (15)."[4]

"Of the [Flowering Locus C] FLC binding sites, 69% contained at least one CArG-box motif with the core consensus sequence CCAAAAAT(G/A)G and an AAA extension at the 3′ end [...]."[4]

Three "other MADS-box flowering-time regulators, SOC1, SVP, and AGAMOUS-LIKE 24 (AGL24), bind to two different CArG-box motifs at 502 bp (CTAAATATGG) and 287 bp (CAATAATTGG) upstream of the translation start in the SEP3 gene (24), consistent with different specificities for the different MADS-box proteins."[4] These together with the core motif CC(A/T)6GG (15) suggest a more general CArG-box motif of (C(C/A/T)(A/T)6(A/G)G).

Smooth muscle cells

"Serum response factor (SRF) controls [smooth muscle cell] SMC gene transcription via binding to CArG box DNA sequences found within genes that exhibit SMC-restricted expression."[2]

"SMC genes examined in this study display SMC-specific histone modifications at the 5′-CArG boxes."[2]

"The SRF-CArG association is required for transcriptional activation of SMC genes [...] the SMC genes examined in this study display SMC-specific histone modifications at the 5′-CArG boxes. [...] enrichment of H4 and H3 acetylation [...] were relatively low from positions –2,800 to –1,600 in the 5′ region. However, at position –1,600 to –1,200, there was a sharp rise in these modifications, which was increased even further at +400 in the coding region. We observed similar patterns for H3K4dMe and H3 Lys79 di-methylation [...]. SRF, TFIID, and RNA polymerase II displayed enrichments that were consistent with the positions of the CArG boxes, TATA box, and coding region, respectively".[2]

The CArG boxes occur between -400 and -200 nts, between the E boxes and the TC elements.[2]

Gene transcriptions

"SMC-restricted binding of SRF to murine SMC gene CArG box chromatin is associated with patterns of posttranslational histone modifications within this chromatin that are specific to the SMC lineage in culture and in vivo, including methylation and acetylation to histone H3 and H4 residues."[2]

Myocardins

The "promyogenic SRF [SRF GeneID: 6722] coactivator myocardin [MYOCD GeneID: 93649] increased SRF association with methylated histones and CArG box chromatin during activation of SMC gene expression. [...] myocardin/SRF complexes physically interact with H3K4dMe and that the interaction of SRF with CArG box chromatin and H3K4dMe is sensitive to expression levels of myocardin."[2]

Kruppel-like factor 4

The "myogenic repressor Kruppel-like factor 4 recruited histone H4 deacetylase activity to SMC genes and blocked SRF association with methylated histones and CArG box chromatin during repression of SMC gene expression. [...] deacetylation of histone H4 coupled with loss of SRF binding during suppression of SMC differentiation in response to vascular injury. [...] KLF4 can bind to evolutionarily conserved TGF-β [control element] (TCE) DNA sequences adjacent to CArG boxes of SM gene promoters"[2]

Epigenomes

"SMC-selective epigenetic control of SRF binding to chromatin plays a key role in regulation of SMC gene expression in response to pathophysiological stimuli in vivo."[2]

Histone modifications in SMCs include H3K4dMe, H3 Lys79 di-methylation, H3 Lys9 acetylation, H4Ac, and SRF binding.[2]

MADS boxes

"RIN [Ripening Inhibitor] binds to DNA sequences known as the CA/T-rich-G (CArG) box, which is the general target of MADS box proteins (Ito et al., 2008)."[5]

Hypotheses

  1. A1BG is not transcribed using a CArG box.

See also

References

  1. Box (disambiguation). San Francisco, California: Wikimedia Foundation, Inc. May 23, 2013. Retrieved 2013-06-15.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 Oliver G. McDonald, Brian R. Wamhoff, Mark H. Hoofnagle, and Gary K. Owens (January 4, 2006). "Control of SRF binding to CArG box chromatin regulates smooth muscle gene expression in vivo". The Journal of Clinical Investigation. 116 (1): 36–48. Retrieved 2014-06-05.
  3. Shinji Kamada and Takeshi Miwa (1 October 1992). "A protein binding to CArG box motifs and to single-stranded DNA functions as a transcriptional repressor". Gene. 119 (2): 229–236. doi:10.1016/0378-1119(92)90276-U. Retrieved 2017-09-17.
  4. 4.0 4.1 4.2 Weiwei Deng, Hua Ying, Chris A. Helliwell, Jennifer M. Taylor, W. James Peacock, and Elizabeth S. Dennis (19 April 2011). "FLOWERING LOCUS C (FLC) regulates development pathways throughout the life cycle of Arabidopsis". Proceedings of the National Academy of Sciences United States of America. 108 (16): 6680–6685. doi:10.1073/pnas.1103175108. Retrieved 2017-09-17.
  5. Masaki Fujisawa, Toshitsugu Nakano, Yoko Shima and Yasuhiro Ito (5 February 2013). "A large-scale identification of direct targets of the tomato MADS box transcription factor RIPENING INHIBITOR reveals the regulation of fruit ripening". The Plant Cell. 25 (2): 371–86. doi:10.1105/tpc.112.108118. Retrieved 2017-02-19.

External links

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