摘要：SummaryHistone methylation, particularly at the H3K4 position, is thought to contribute to the specification of photoreceptor cell fate; however, the mechanisms linking histone methylation with transcription factor transactivation and photoreceptor gene expression have not yet been determined. Here, we demonstrate that MLL5 is abundantly expressed in the mouse retina. Mll5 deficiency impaired electroretinogram responses, alongside attenuated expression of a number of retina genes. Mechanistic studies revealed that MLL5 interacts with the retina-specific transcription factor, CRX, contributing to its binding to photoreceptor-specific gene promoters. Moreover, depletion of MLL5 impairs H3K4 methylation and H3K79 methylation, which subsequently compromises CRX-CBP assembly and H3 acetylation on photoreceptor promoters. Our data support a scenario in which recognition of H3K4 methylation by MLL5 is required for photoreceptor-specific gene transcription through maintaining a permissive chromatin state and proper CRX-CBP recruitment at promoter sites.Graphical abstractDisplay OmittedHighlights•MLL5 is essential for the expression of critical photoreceptor genes•MLL5 depletion reduces H3K4/K79 methylation at photoreceptor gene promoters•MLL5 interacts with CRX via its CD4 domain•Recognition of H3K4me2/3 by MLL5 is a prerequisite for CRX recruitment to chromatinBiological sciences; Molecular biology; Neuroscience; Molecular neuroscience; Omics
