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...
Autores principales: | , , , , |
---|---|
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 |