Transcription coactivators p300 and CBP are necessary for photoreceptor-specific chromatin organization and gene expression.

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 regu...

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Autores principales:	Anne K Hennig, Guang-Hua Peng, Shiming Chen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7338bd1150614c6c8d43d532dcf30040
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spelling	oai:doaj.org-article:7338bd1150614c6c8d43d532dcf300402021-11-18T09:02:43ZTranscription coactivators p300 and CBP are necessary for photoreceptor-specific chromatin organization and gene expression.1932-620310.1371/journal.pone.0069721https://doaj.org/article/7338bd1150614c6c8d43d532dcf300402013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23922782/?tool=EBIhttps://doaj.org/toc/1932-6203Rod 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.Anne K HennigGuang-Hua PengShiming ChenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e69721 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anne K Hennig Guang-Hua Peng Shiming Chen Transcription coactivators p300 and CBP are necessary for photoreceptor-specific chromatin organization and gene expression.
description	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.
format	article
author	Anne K Hennig Guang-Hua Peng Shiming Chen
author_facet	Anne K Hennig Guang-Hua Peng Shiming Chen
author_sort	Anne K Hennig
title	Transcription coactivators p300 and CBP are necessary for photoreceptor-specific chromatin organization and gene expression.
title_short	Transcription coactivators p300 and CBP are necessary for photoreceptor-specific chromatin organization and gene expression.
title_full	Transcription coactivators p300 and CBP are necessary for photoreceptor-specific chromatin organization and gene expression.
title_fullStr	Transcription coactivators p300 and CBP are necessary for photoreceptor-specific chromatin organization and gene expression.
title_full_unstemmed	Transcription coactivators p300 and CBP are necessary for photoreceptor-specific chromatin organization and gene expression.
title_sort	transcription coactivators p300 and cbp are necessary for photoreceptor-specific chromatin organization and gene expression.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/7338bd1150614c6c8d43d532dcf30040
work_keys_str_mv	AT annekhennig transcriptioncoactivatorsp300andcbparenecessaryforphotoreceptorspecificchromatinorganizationandgeneexpression AT guanghuapeng transcriptioncoactivatorsp300andcbparenecessaryforphotoreceptorspecificchromatinorganizationandgeneexpression AT shimingchen transcriptioncoactivatorsp300andcbparenecessaryforphotoreceptorspecificchromatinorganizationandgeneexpression
_version_	1718420970230775808

Transcription coactivators p300 and CBP are necessary for photoreceptor-specific chromatin organization and gene expression.

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