7n27

Structural highlights

Function

CDYL_HUMAN Chromatin reader protein that recognizes and binds histone H3 trimethylated at 'Lys-9', dimethylated at 'Lys-27' and trimethylated at 'Lys-27' (H3K9me3, H3K27me2 and H3K27me3, respectively) (PubMed:19808672, PubMed:28402439). Part of multimeric repressive chromatin complexes, where it is required for transmission and restoration of repressive histone marks, thereby preserving the epigenetic landscape (PubMed:28402439). Required for chromatin targeting and maximal enzymatic activity of Polycomb repressive complex 2 (PRC2); acts as a positive regulator of PRC2 activity by bridging the pre-existing histone H3K27me3 and newly recruited PRC2 on neighboring nucleosomes (PubMed:22009739). Acts as a corepressor for REST by facilitating histone-lysine N-methyltransferase EHMT2 recruitment and H3K9 dimethylation at REST target genes for repression (PubMed:19061646). Involved in X chromosome inactivation in females: recruited to Xist RNA-coated X chromosome and facilitates propagation of H3K9me2 by anchoring EHMT2 (By similarity). Promotes EZH2 accumulation and H3K27me3 methylation at DNA double strand breaks (DSBs), thereby facilitating transcriptional repression at sites of DNA damage and homology-directed repair of DSBs (PubMed:29177481). Required for neuronal migration during brain development by repressing expression of RHOA (By similarity). By repressing the expression of SCN8A, contributes to the inhibition of intrinsic neuronal excitability and epileptogenesis (By similarity). In addition to acting as a chromatin reader, acts as a hydro-lyase (PubMed:28803779). Shows crotonyl-coA hydratase activity by mediating the conversion of crotonyl-CoA ((2E)-butenoyl-CoA) to beta-hydroxybutyryl-CoA (3-hydroxybutanoyl-CoA), thereby acting as a negative regulator of histone crotonylation (PubMed:28803779). Histone crotonylation is required during spermatogenesis; down-regulation of histone crotonylation by CDYL regulates the reactivation of sex chromosome-linked genes in round spermatids and histone replacement in elongating spermatids (By similarity). By regulating histone crotonylation and trimethylation of H3K27, may be involved in stress-induced depression-like behaviors, possibly by regulating VGF expression (By similarity).[UniProtKB:Q9WTK2]^{[1] [2] [3] [4] [5] [6]} Not able to recognize and bind histone H3K9me3, histone H3K27me2 and histone H3K27me3, due to the presence of a N-terminal extension that inactivates the chromo domain (PubMed:19808672).^[7] Not able to recognize and bind histone H3K9me3, histone H3K27me2 and histone H3K27me3, due to the absence of the chromo domain (PubMed:19808672). Acts as a negative regulator of isoform 2 by displacing isoform 2 from chromatin.^[8]

References

1. ↑ Mulligan P, Westbrook TF, Ottinger M, Pavlova N, Chang B, Macia E, Shi YJ, Barretina J, Liu J, Howley PM, Elledge SJ, Shi Y. CDYL bridges REST and histone methyltransferases for gene repression and suppression of cellular transformation. Mol Cell. 2008 Dec 5;32(5):718-26. PMID:19061646 doi:10.1016/j.molcel.2008.10.025
2. ↑ Franz H, Mosch K, Soeroes S, Urlaub H, Fischle W. Multimerization and H3K9me3 binding are required for CDYL1b heterochromatin association. J Biol Chem. 2009 Dec 11;284(50):35049-59. PMID:19808672 doi:10.1074/jbc.M109.052332
3. ↑ Zhang Y, Yang X, Gui B, Xie G, Zhang D, Shang Y, Liang J. Corepressor protein CDYL functions as a molecular bridge between polycomb repressor complex 2 and repressive chromatin mark trimethylated histone lysine 27. J Biol Chem. 2011 Dec 9;286(49):42414-42425. PMID:22009739 doi:10.1074/jbc.M111.271064
4. ↑ Liu Y, Liu S, Yuan S, Yu H, Zhang Y, Yang X, Xie G, Chen Z, Li W, Xu B, Sun L, Shang Y, Liang J. Chromodomain protein CDYL is required for transmission/restoration of repressive histone marks. J Mol Cell Biol. 2017 Jun 1;9(3):178-194. PMID:28402439 doi:10.1093/jmcb/mjx013
5. ↑ Liu S, Yu H, Liu Y, Liu X, Zhang Y, Bu C, Yuan S, Chen Z, Xie G, Li W, Xu B, Yang J, He L, Jin T, Xiong Y, Sun L, Liu X, Han C, Cheng Z, Liang J, Shang Y. Chromodomain Protein CDYL Acts as a Crotonyl-CoA Hydratase to Regulate Histone Crotonylation and Spermatogenesis. Mol Cell. 2017 Sep 7;67(5):853-866.e5. PMID:28803779 doi:10.1016/j.molcel.2017.07.011
6. ↑ Abu-Zhayia ER, Awwad SW, Ben-Oz BM, Khoury-Haddad H, Ayoub N. CDYL1 fosters double-strand break-induced transcription silencing and promotes homology-directed repair. J Mol Cell Biol. 2018 Aug 1;10(4):341-357. PMID:29177481 doi:10.1093/jmcb/mjx050
7. ↑ Franz H, Mosch K, Soeroes S, Urlaub H, Fischle W. Multimerization and H3K9me3 binding are required for CDYL1b heterochromatin association. J Biol Chem. 2009 Dec 11;284(50):35049-59. PMID:19808672 doi:10.1074/jbc.M109.052332
8. ↑ Franz H, Mosch K, Soeroes S, Urlaub H, Fischle W. Multimerization and H3K9me3 binding are required for CDYL1b heterochromatin association. J Biol Chem. 2009 Dec 11;284(50):35049-59. PMID:19808672 doi:10.1074/jbc.M109.052332