Cargando…

ZNF750 interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes

ZNF750 controls epithelial homeostasis by inhibiting progenitor genes while inducing differentiation genes, a role underscored by pathogenic ZNF750 mutations in cancer and psoriasis. How ZNF750 accomplishes these dual gene regulatory impacts is unknown. Here, we characterized ZNF750 as a transcripti...

Descripción completa

Detalles Bibliográficos
Autores principales: Boxer, Lisa D., Barajas, Brook, Tao, Shiying, Zhang, Jiajing, Khavari, Paul A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173152/
https://www.ncbi.nlm.nih.gov/pubmed/25228645
http://dx.doi.org/10.1101/gad.246579.114
_version_ 1782336140032868352
author Boxer, Lisa D.
Barajas, Brook
Tao, Shiying
Zhang, Jiajing
Khavari, Paul A.
author_facet Boxer, Lisa D.
Barajas, Brook
Tao, Shiying
Zhang, Jiajing
Khavari, Paul A.
author_sort Boxer, Lisa D.
collection PubMed
description ZNF750 controls epithelial homeostasis by inhibiting progenitor genes while inducing differentiation genes, a role underscored by pathogenic ZNF750 mutations in cancer and psoriasis. How ZNF750 accomplishes these dual gene regulatory impacts is unknown. Here, we characterized ZNF750 as a transcription factor that binds both the progenitor and differentiation genes that it controls at a CCNNAGGC DNA motif. ZNF750 interacts with the pluripotency transcription factor KLF4 and chromatin regulators RCOR1, KDM1A, and CTBP1/2 through conserved PLNLS sequences. ChIP-seq (chromatin immunoprecipitation [ChIP] followed by high-throughput sequencing) and gene depletion revealed that KLF4 colocalizes ∼10 base pairs from ZNF750 at differentiation target genes to facilitate their activation but is unnecessary for ZNF750-mediated progenitor gene repression. In contrast, KDM1A colocalizes with ZNF750 at progenitor genes and facilitates their repression but is unnecessary for ZNF750-driven differentiation. ZNF750 thus controls differentiation in concert with RCOR1 and CTBP1/2 by acting with either KDM1A to repress progenitor genes or KLF4 to induce differentiation genes.
format Online
Article
Text
id pubmed-4173152
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Cold Spring Harbor Laboratory Press
record_format MEDLINE/PubMed
spelling pubmed-41731522015-03-15 ZNF750 interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes Boxer, Lisa D. Barajas, Brook Tao, Shiying Zhang, Jiajing Khavari, Paul A. Genes Dev Research Paper ZNF750 controls epithelial homeostasis by inhibiting progenitor genes while inducing differentiation genes, a role underscored by pathogenic ZNF750 mutations in cancer and psoriasis. How ZNF750 accomplishes these dual gene regulatory impacts is unknown. Here, we characterized ZNF750 as a transcription factor that binds both the progenitor and differentiation genes that it controls at a CCNNAGGC DNA motif. ZNF750 interacts with the pluripotency transcription factor KLF4 and chromatin regulators RCOR1, KDM1A, and CTBP1/2 through conserved PLNLS sequences. ChIP-seq (chromatin immunoprecipitation [ChIP] followed by high-throughput sequencing) and gene depletion revealed that KLF4 colocalizes ∼10 base pairs from ZNF750 at differentiation target genes to facilitate their activation but is unnecessary for ZNF750-mediated progenitor gene repression. In contrast, KDM1A colocalizes with ZNF750 at progenitor genes and facilitates their repression but is unnecessary for ZNF750-driven differentiation. ZNF750 thus controls differentiation in concert with RCOR1 and CTBP1/2 by acting with either KDM1A to repress progenitor genes or KLF4 to induce differentiation genes. Cold Spring Harbor Laboratory Press 2014-09-15 /pmc/articles/PMC4173152/ /pubmed/25228645 http://dx.doi.org/10.1101/gad.246579.114 Text en © 2014 Boxer et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Boxer, Lisa D.
Barajas, Brook
Tao, Shiying
Zhang, Jiajing
Khavari, Paul A.
ZNF750 interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes
title ZNF750 interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes
title_full ZNF750 interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes
title_fullStr ZNF750 interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes
title_full_unstemmed ZNF750 interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes
title_short ZNF750 interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes
title_sort znf750 interacts with klf4 and rcor1, kdm1a, and ctbp1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173152/
https://www.ncbi.nlm.nih.gov/pubmed/25228645
http://dx.doi.org/10.1101/gad.246579.114
work_keys_str_mv AT boxerlisad znf750interactswithklf4andrcor1kdm1aandctbp12chromatinregulatorstorepressepidermalprogenitorgenesandinducedifferentiationgenes
AT barajasbrook znf750interactswithklf4andrcor1kdm1aandctbp12chromatinregulatorstorepressepidermalprogenitorgenesandinducedifferentiationgenes
AT taoshiying znf750interactswithklf4andrcor1kdm1aandctbp12chromatinregulatorstorepressepidermalprogenitorgenesandinducedifferentiationgenes
AT zhangjiajing znf750interactswithklf4andrcor1kdm1aandctbp12chromatinregulatorstorepressepidermalprogenitorgenesandinducedifferentiationgenes
AT khavaripaula znf750interactswithklf4andrcor1kdm1aandctbp12chromatinregulatorstorepressepidermalprogenitorgenesandinducedifferentiationgenes