CDYL
Description
The CDYL (chromodomain Y like) is a protein-coding gene located on chromosome 6.
CDYL isoform 2 acts as a chromatin reader protein recognizing and binding histone H3 trimethylated at Lys-9, dimethylated at Lys-27 and trimethylated at Lys-27. This protein is a part of multimeric repressive chromatin complexes and plays a crucial role in transmission and restoration of repressive histone marks, thus preserving the epigenetic landscape. CDYL isoform 2 is required for chromatin targeting and maximal enzymatic activity of Polycomb repressive complex 2 (PRC2), functioning as a positive regulator of PRC2 activity by bridging pre-existing histone H3K27me3 and newly recruited PRC2 on neighboring nucleosomes. It acts as a corepressor for REST by facilitating histone-lysine N-methyltransferase EHMT2 recruitment and H3K9 dimethylation at REST target genes for repression. CDYL isoform 2 is involved in X chromosome inactivation in females, being recruited to Xist RNA-coated X chromosome and facilitating propagation of H3K9me2 by anchoring EHMT2. This isoform promotes EZH2 accumulation and H3K27me3 methylation at DNA double strand breaks (DSBs), contributing to transcriptional repression at sites of DNA damage and homology-directed repair of DSBs. It is required for neuronal migration during brain development by repressing expression of RHOA. CDYL isoform 2 represses the expression of SCN8A, leading to the inhibition of intrinsic neuronal excitability and epileptogenesis. Beyond its role as a chromatin reader, CDYL isoform 2 acts as a hydro-lyase. It exhibits crotonyl-coA hydratase activity by mediating the conversion of crotonyl-CoA to beta-hydroxybutyryl-CoA, serving as a negative regulator of histone crotonylation. Histone crotonylation is essential 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. Through regulating histone crotonylation and trimethylation of H3K27, CDYL isoform 2 might be involved in stress-induced depression-like behaviors, potentially by regulating VGF expression.
CDYL is also known as CDYL1.
Associated Diseases
- multiple sclerosis
- Parkinson disease
- lysosomal storage disease
- Alzheimer disease
- liver and intrahepatic bile duct neoplasm
- Miyoshi myopathy
