Epigenetic regulation, including DNA methylation, histone modifications, and chromatin remodeling, play an important role in the nervous system. However, the role of epigenetic mechanisms contribute to dendrite morphogenesis is nearly unknown.
Chromodomain Y-like (CDYL) protein, containing an N-terminal chromodomain has been implicated in transcription repression. CDYL connects the transcription repressor RE1- silencing transcription factor (REST) and the histone H3K9 methyltransferase G9a for repression of gene transcription.
This study report that CDYL is a negative regulator of dendrite branching. CDYL recruits the H3K27methyltransferase activity to the brain-derived neurotropic factor (BDNF) promoter to regulate gene transcription and, CDYL and EZH2 coordinately regulate dendrite morphogenesis. During KCl stimulation, Neuronal CDYL protein is rapidly degraded indicating that CDYL is an important regulator of dendrite morphogenesis in activity-dependent neuronal function. In cultured primary hippocampal neurons, overexpression of CDYL reduces the dendritic arborization and total dendritic branch length; on the other hand, knock-down of CDYL increases the dendritic complexity, which could be reduced by overexpression of a shRNA-resistant CDYL construct.
To summary, CDYL functions as a reader protein for histone modifications and participates in the establishment of the repressive histone methylation marks in chromatin. Furthermore, these mechanistic studies may offer better therapeutic opportunities for neurological diseases in the future.