Grainy head gene transcriptions

Associate Editor(s)-in-Chief: Henry A. Hoff

"The defined GRHL1 DNA‐binding consensus sequence (AACCGGTT) was identical to that defined for GRHL3, and also matched the consensus sequence for Drosophila GRH DNA binding, which we had previously identified by alignment of multiple GRH‐responsive gene regulatory regions (Wilanowski et al, 2002; Ting et al, 2005). Of note, the first of the two cytosines and the second of the guanines were invariant in both GRHL1 and GRHL3 CASTing assays."

"The putative GRHL1‐binding motif (GACTGGTT) is perfectly conserved, together with 6 bp upstream and 12 bp downstream flanking sequences, in three of the Dsg1 promoters: mouse Dsg1α, mouse Dsg1γ, and human DSG1 [...]. In the mouse Dsg1β promoter, this motif is slightly different (AACTGGTT), although the flanking sequences are still conserved."

"The consensus DNA‐binding sequence identified for GRHL1 is identical to that defined for Drosophila GRH (Wilanowski et al, 2002). In addition, the identification of cadherin genes as direct transcriptional targets of GRHL1 extends the links between the grh and cadherin gene families from Drosophila to mammals. The cadherin family consists of more than 100 members (including the protocadherins) involved in many diverse cellular and developmental events (Nollet et al, 2000). Among the known targets of Drosophila, GRH are two cadherin superfamily members, stan/fmi and E‐cadherin/shotgun (Lee and Adler, 2004; Almeida and Bray, 2005). The links between the two gene families have recently been extended in another model organism. A study of genome‐wide predictions of genetic interactions in C. elegans has identified a number of cadherin family members as prime targets for significant functional interactions with Grh‐1, the worm homologue of grh (Zhong and Sternberg, 2006). These included cdh‐6, a homologue of Drosophila stan, and hmp‐2, a β‐catenin. We have recently identified the mammalian homologue of E‐cadherin as a target of another member of the Grh‐like family, Grhl2 (JMC and SMJ, unpublished)."

Human genes

Gene ID: 999 is CDH1 cadherin 1: "This gene encodes a classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid and ovarian cancer. Loss of function of this gene is thought to contribute to cancer progression by increasing proliferation, invasion, and/or metastasis. The ectodomain of this protein mediates bacterial adhesion to mammalian cells and the cytoplasmic domain is required for internalization. This gene is present in a gene cluster with other members of the cadherin family on chromosome 16."

1. NP_001304113.1 cadherin-1 isoform 2 precursor: "Transcript Variant: This variant (2) lacks an alternate exon in the central coding region compared to variant 1. The encoded isoform (2) is shorter than isoform 1. This isoform (2) may undergo proteolytic processing similar to isoform 1."
2. NP_001304114.1 cadherin-1 isoform 3: "Transcript Variant: This variant (3) uses an alternate splice site in an exon in its 5' UTR, resulting in a different 5' UTR and the use of a downstream start site compared to variant 1. The encoded isoform (3) has a shorter N-terminus and lacks a predicted signal peptide compared to isoform 1."
3. NP_001304115.1 cadherin-1 isoform 4: "Transcript Variant: This variant (4) lacks an exon in its 5' UTR, resulting in a different 5' UTR and the use of a downstream start site compared to variant 1. The encoded isoform (4) has a shorter N-terminus and lacks a predicted signal peptide compared to isoform 1."
4. NP_004351.1 cadherin-1 isoform 1 preproprotein: "Transcript Variant: This variant (1) encodes the longest isoform (1)."

Gene ID: 1000 is CDH2 cadherin 2: "This gene encodes a classical cadherin and member of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein is proteolytically processed to generate a calcium-dependent cell adhesion molecule and glycoprotein. This protein plays a role in the establishment of left-right asymmetry, development of the nervous system and the formation of cartilage and bone."

1. NP_001295105.1 cadherin-2 isoform 2: "Transcript Variant: This variant (2) represents use of an alternate promoter, and therefore differs in the 5' UTR and 5' coding region, compared to variant 1. These differences cause translation initiation at an alternate start codon, resulting in an isoform (2) that lacks a predicted signal peptide and has a distinct N-terminus compared to isoform 1."
2. NP_001783.2 cadherin-2 isoform 1 preproprotein: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."

Gene ID: 1001 is CDH3 cadherin 3: "This gene encodes a classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. This gene is located in a gene cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer. In addition, aberrant expression of this protein is observed in cervical adenocarcinomas. Mutations in this gene are associated with hypotrichosis with juvenile macular dystrophy and ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome (EEMS)."

1. NP_001304124.1 cadherin-3 isoform 2 precursor: "Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region, which results in a frameshift and an early stop codon. The encoded isoform (2) has a shorter and distinct C-terminus compared to isoform 1. This isoform (2) may undergo proteolytic processing similar to isoform (1)."
2. NP_001304125.1 cadherin-3 isoform 3: "Transcript Variant: This variant (3) lacks an alternate exon in its 5' UTR, resulting in the use of a downstream translation start site compared to variant 1. The encoded isoform (3) has a shorter N-terminus and lacks a predicted signal peptide compared to isoform 1."
3. NP_001784.2 cadherin-3 isoform 1 preproprotein": "Transcript Variant: This variant (1) encodes the longest isoform (1)."

Gene ID: 1002 is CDH4 cadherin 4: "This gene is a classical cadherin from the cadherin superfamily. The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Based on studies in chicken and mouse, this cadherin is thought to play an important role during brain segmentation and neuronal outgrowth. In addition, a role in kidney and muscle development is indicated. Of particular interest are studies showing stable cis-heterodimers of cadherins 2 and 4 in cotransfected cell lines. Previously thought to interact in an exclusively homophilic manner, this is the first evidence of cadherin heterodimerization. Three transcript variants encoding different isoforms have been found for this gene."

See also

• Cadherin
• Transcription factor