Transcription Coactivators p300 and CBP Are Necessary for Photoreceptor-Specific Chromatin Organization and Gene Expression

Abstract

Rod and cone photoreceptor neurons in the mammalian retina possess specialized cellular architecture and functional features for converting light to a neuronal signal. Establishing and maintaining these characteristics requires appropriate expression of a specific set of genes, which is tightly regulated by a network of photoreceptor transcription factors centered on the cone-rod homeobox protein CRX. CRX recruits transcription coactivators p300 and CBP to acetylate promoter-bound histones and activate transcription of target genes. To further elucidate the role of these two coactivators, we conditionally knocked out Ep300 and/or CrebBP in differentiating rods or cones, using opsin-driven Cre recombinase. Knockout of either factor alone exerted minimal effects, but loss of both factors severely disrupted target cell morphology and function: the unique nuclear chromatin organization seen in mouse rods was reversed, accompanied by redistribution of nuclear territories associated with repressive and active histone marks. Transcription of many genes including CRX targets was severely impaired, correlating with reduced histone H3/H4 acetylation (the products of p300/CBP) on target gene promoters. Interestingly, the presence of a single wild-type allele of either coactivator prevented many of these defects, with Ep300 more effective than Cbp. These results suggest that p300 and CBP play essential roles in maintaining photoreceptor-specific structure, function and gene expression.

Nrl‐Cre transgenic mouse mediates loxP recombination in developing rod photoreceptors

“…This recombination time course is consistent with the temporal expression pattern of endogenous Nrl in developing rods (Akimoto, 2006). In contrast, Cre‐mediated recombination in Rho‐Cre and Cone‐Cre mice starts later than P5 in differentiated rods or cones and is incomplete until P12 (Hennig et al ., ; Le et al ., , Li et al ., ).…”

Knock‐down of p300 decreases the proliferation and odontogenic differentiation potentiality of HDPCs

“…, Henning et al . ). It might regulate the histone acetylation of the odontogenic markers or specific transcription factor(s), and thus, promoted the transcription of these genes.…”

NAMPT-Mediated NAD+ Biosynthesis Is Essential for Vision In Mice

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