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Publication : MLL5 is involved in retinal photoreceptor maturation through facilitating CRX-mediated photoreceptor gene transactivation.

First Author  Zhang X Year  2022
Journal  iScience Volume  25
Issue  4 Pages  104058
PubMed ID  35359806 Mgi Jnum  J:337231
Mgi Id  MGI:7259658 Doi  10.1016/j.isci.2022.104058
Citation  Zhang X, et al. (2022) MLL5 is involved in retinal photoreceptor maturation through facilitating CRX-mediated photoreceptor gene transactivation. iScience 25(4):104058
abstractText  Histone 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.
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