Alternative titles; symbols
HGNC Approved Gene Symbol: CDY1
Cytogenetic location: Yq11.23 Genomic coordinates (GRCh38) : Y:25,622,115-25,625,511 (from NCBI)
CDY family proteins, such as CDY1, each contain a chromodomain and catalytic domain that are highly conserved and implicated in histone modification and recognition. However, due to subtle amino acid changes in their chromodomains, CDY proteins display substantial differences in chromatin recognition and binding, thereby diversifying the epigenetic regulatory roles they play (Fischle et al., 2008).
Lahn and Page (1997) isolated testis cDNAs corresponding to CDY (chromodomain on Y chromosome) and other genes located in the nonrecombining portion of the Y chromosome (NRY). The predicted CDY protein contains a chromodomain (see 603079) and a putative catalytic domain. The authors noted that CDY was 1 of 7 novel genes that appeared to exist in multiple copies on the Y chromosome and were expressed specifically in testis. See BPY1 (400012).
Lahn and Page (1999) isolated 2 distinct species of CDY cDNAs from testis, CDY1 and CDY2 (400018). The predicted 540-amino acid CDY1 protein is 98% identical to CDY2. These authors also isolated a minor, alternatively spliced CDY1 transcript encoding a 554-amino acid isoform with a divergent C terminus. The CDY1 gene coding region corresponding to the major transcript does not contain any introns, although a single intron is excised to form the minor mRNA. The authors stated that there might be multiple CDY1 and CDY2 genes. They proposed that these Y-linked CDY genes arose by retroposition of an mRNA from the autosomal CDYL (603778) gene, followed by amplification of the retroposed gene. Since no Y-linked CDY homolog was found in the mouse, Lahn and Page (1999) suggested that CDYL may have given rise to CDY some time after the divergence of the mouse and human lineages.
Fischle et al. (2008) showed that FLAG-tagged human CDY and CDYL and mouse Cdyl2 (618816) localized exclusively in nuclei of mouse fibroblasts. Cdyl2 was found throughout nucleus in a punctate distribution pattern and colocalized with regions of trimethylated histone H3 (see 602810) lys9 (H3K9me3). CDY was excluded from nucleoli, but overlapped in chromatin with regions of H3K9me3. CDYL was also excluded from nucleoli, but it did not overlap with regions of H3K9me3.
By analysis of a panel of partial Y chromosomes, Lahn and Page (1997) found that CDY genes mapped to both the 6F and 5L regions on the long arm of the human Y chromosome. Using the same technique, Lahn and Page (1999) mapped the CDY1 gene to the Y-chromosome 6F region. Yen (1998) detected 2 CDY genes in deletion interval 6 of the human Y chromosome.
Gross (2020) mapped the CDY1 gene to chromosome Yq11.23 based on an alignment of the CDY1 sequence (GenBank BC132955) with the genomic sequence (GRCh38).
Fischle et al. (2008) noted that the chromodomain of human CDY interacts with methylated H3K9. They found that, despite their high homology and similar tertiary structures, the chromodomains of CDY, CDYL, and CDYL2 displayed variability in binding to H3K9me3. Both the CDY and CDYL2 chromodomains bound to a similar fragment of the H3 tail, but the CDY chromodomain bound more avidly than the CDYL2 chromodomain. The CDY and CDYL2 chromodomains also displayed different sensitivities to H3K9 methylation level. The affinity of the CDYL2 chromodomain increased with methylation level, whereas binding of the CDY chromodomain to the H3K9me1 peptide was as efficient as binding of the CDYL2 chromodomain to the H3K9me3 peptide. Phosphorylation of ser10 adjacent to H3K9 weakened binding of CDY and CDYL2 to the H3K9me3 peptide. The CDYL chromodomain did not bind to the H3K9me3 peptide, but efficient binding could be established by point mutations in the chromodomain. In addition to H3K9me3, other lysine-methylated binding sites were identified for the CDY and CDYL2 chromodomains, but the CDY chromodomain displayed substantially higher selectivity for binding compared with the CDYL2 chromodomain.
Repping et al. (2004) identified the b2/b3 deletion within the AZFc region (415000) of the Y chromosome, in which 1 of the 2 copies of the CDY1 gene is deleted. The b2/b3 deletion has no obvious effect on fitness.
To determine the incidence of various partial AZFc deletions and their effect on fertility, Machev et al. (2004) discriminated 4 types of DAZ-CDY1 partial deletions and performed combined quantitative and qualitative analyses of the AZFc region in 300 infertile men and 399 controls. Only one deletion type, DAZ3/4 (400027, 400003)-CDY1a, was associated with male infertility (p = 0.042), suggesting that most of the partial deletions are neutral variants. A stronger association, however, was found between loss of the CDY1a sequence family variant (SFV) and infertility (p = 0.002). Machev et al. (2004) concluded that loss of this SFV through deletion or gene conversion could be a major risk factor for male infertility.
Dorus et al. (2003) showed that the progenitor of the CDY gene family arose de novo in the mammalian ancestor via domain accretion. This progenitor later duplicated to generate CDYL and CDYL2, 2 autosomal genes found in all extant mammals. Prior to human-mouse divergence, a processed CDYL transcript retroposed onto the Y chromosome to create CDY. In the simian lineage, CDY was retained and subsequently amplified on the Y. In nonsimian mammals, however, CDY appears to have been lost. The retention of the Y-linked CDY genes in simians spurred the process of subfunctionalization and possibly neofunctionalization. Subfunctionalization is evidenced by the observation that simian CDYL and CDYL2 retained their somatic housekeeping transcripts but lost the spermatogenic transcripts to the newly arisen CDY. Neofunctionalization is suggested by the rapid evolution of the CDY protein sequence. Dorus et al. (2003) concluded that the CDY-related family offers an example of how duplicated genes undergo functional diversification in both expression profile and protein sequence and supports the hypothesis that there is a tendency for spermatogenic functions to transfer from autosomes to the Y chromosome.
Dorus, S., Gilbert, S. L., Forster, M. L., Barndt, R. J., Lahn, B. T. The CDY-related gene family: coordinated evolution in copy number, expression profile and protein sequence. Hum. Molec. Genet. 12: 1643-1650, 2003. [PubMed: 12837688] [Full Text: https://doi.org/10.1093/hmg/ddg185]
Fischle, W., Franz, H., Jacobs, S. A., Allis, C. D., Khorasanizadeh, S. Specificity of the chromodomain Y chromosome family of chromodomains for lysine-methylated ARK(S/T) motifs. J. Biol. Chem. 283: 19626-19635, 2008. [PubMed: 18450745] [Full Text: https://doi.org/10.1074/jbc.M802655200]
Gross, M. B. Personal Communication. Baltimore, Md. 3/17/2020.
Lahn, B. T., Page, D. C. Functional coherence of the human Y chromosome. Science 278: 675-680, 1997. [PubMed: 9381176] [Full Text: https://doi.org/10.1126/science.278.5338.675]
Lahn, B. T., Page, D. C. Retroposition of autosomal mRNA yielded testis-specific gene family on human Y chromosome. Nature Genet. 21: 429-433, 1999. Note: Erratum: Nature Genet. 22: 209 only, 1999. [PubMed: 10192397] [Full Text: https://doi.org/10.1038/7771]
Machev, N., Saut, N., Longepied, G., Terriou, P., Navarro, A., Levy, N., Guichaoua, M., Metzler-Guillemain, C., Collignon, P., Frances, A.-M., Belougne, J., Clemente, E., Chiaroni, J., Chevillard, C., Durand, C., Ducourneau, A., Pech, N., McElreavey, K., Mattei, M.-G., Mitchell, M. J. Sequence family variant loss from the AZFc interval of the human Y chromosome, but not gene copy loss, is strongly associated with male infertility. J. Med. Genet. 41: 814-825, 2004. Note: Erratum: J. Med. Genet. 41: 960 only, 2004. [PubMed: 15520406] [Full Text: https://doi.org/10.1136/jmg.2004.022111]
Repping, S., van Daalen, S. K. M., Korver, C. M., Brown, L. G., Marszalek, J. D., Gianotten, J., Oates, R. D., Silber, S., van der Veen, F., Page, D. C., Rozen, S. A family of human Y chromosomes has dispersed throughout northern Eurasia despite a 1.8-Mb deletion in the azoospermia factor c region. Genomics 83: 1046-1052, 2004. [PubMed: 15177557] [Full Text: https://doi.org/10.1016/j.ygeno.2003.12.018]
Yen, P. H. A long-range restriction map of deletion interval 6 of the human Y chromosome: a region frequently deleted in azoospermic males. Genomics 54: 5-12, 1998. [PubMed: 9806824] [Full Text: https://doi.org/10.1006/geno.1998.5526]