ZNF750 interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes.
ZNF750 interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes.
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ZnF750与KLF4和RCOR1，KDM1A和CTBP1/2染色质调节剂相互作用，以抑制表皮祖细胞基因并诱导分化基因。
DOI：
10.1101/gad.246579.114
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发表时间：
2014-09-15
影响因子：
10.5
通讯作者：
Khavari PA
中科院分区：
文献类型：
--
作者：
Boxer LD;Barajas B;Tao S;Zhang J;Khavari PA
ZNF 750通过抑制祖细胞基因而诱导分化基因来控制上皮细胞的稳态。Boxer等人将ZNF 750描述为一种转录因子，它在CCNNAGGC DNA基序处控制祖细胞和分化基因。ZNF 750与RCOR 1和CTBP 1/2协同作用，通过与KDM 1A抑制祖细胞基因或KLF 4诱导分化基因来控制分化。ZNF750通过抑制祖基因同时诱导分化基因来控制上皮细胞的稳态，这一作用在癌症和银屑病中的致病性ZNF750突变中得到了强调。ZNF 750如何实现这些双重基因调控影响尚不清楚。在这里，我们的特点ZNF 750作为一个转录因子，结合祖细胞和分化基因，它控制在一个CCNNAGGC DNA基序。ZNF 750通过保守的PLNLS序列与多能性转录因子KLF 4和染色质调节因子RCOR 1、KDM 1A和CTBP 1/2相互作用。ChIP-seq（染色质免疫沉淀[ChIP]，然后进行高通量测序）和基因缺失显示，KLF4在分化靶基因处共定位来自ZNF 750的10个碱基对，以促进其激活，但对于ZNF 750介导的祖基因抑制是不必要的。相反，KDM1A与ZNF750共定位于祖基因，并促进它们的抑制，但对ZNF750驱动的分化是不必要的。ZNF 750与RCOR 1和CTBP 1/2协同作用，通过与KDM 1A抑制祖细胞基因或与KLF 4诱导分化基因来控制分化。
ZNF750 controls epithelial homeostasis by inhibiting progenitor genes while inducing differentiation genes. Here, Boxer et al. characterized ZNF750 as a transcription factor that binds both the progenitor and differentiation genes that it controls at a CCNNAGGC DNA motif. ZNF750 controls differentiation in concert with RCOR1 and CTBP1/2 by acting with either KDM1A to repress progenitor genes or KLF4 to 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 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.
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影响因子：
--
作者：
Paliwal, Seema;Ho, Ngoc;Grossman, Steven R
通讯作者：
Grossman, Steven R
影响因子：
64.8
作者：
Lee, MG;Wynder, C;Shiekhattar, R
通讯作者：
Shiekhattar, R
影响因子：
21.3
作者：
Jiang, Jianming;Chan, Yun-Shen;Ng, Huck-Hui
通讯作者：
Ng, Huck-Hui
DOI：
10.1073/pnas.96.12.6683
发表时间：
1999-06-08
影响因子：
11.1
作者：
Postigo, AA;Dean, DC
通讯作者：
Dean, DC
影响因子：
11.4
作者：
Feinberg, Mark W.;Wara, Akm Khyrul;Jain, Mukesh K.
通讯作者：
Jain, Mukesh K.