Atypical GATA transcription factor TRPS1 represses gene expression by recruiting CHD4/NuRD(MTA2) and suppresses cell migration and invasion by repressing TP63 expression

Transcriptional repressor GATA binding 1 (TRPS1), an atypical GATA transcription factor, functions as a transcriptional repressor and is also implicated in human cancers. However, the underlying mechanism of TRPS1 contributing to malignancy remains obscure. In the current study, we report that TRPS1...

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Autores principales: Wang, Yuzhi, Lin, Xue, Gong, Xue, Wu, Lele, Zhang, Jun, Liu, Weiguang, Li, Jian, Chen, Liming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299095/
https://www.ncbi.nlm.nih.gov/pubmed/30563971
http://dx.doi.org/10.1038/s41389-018-0108-9
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author Wang, Yuzhi
Lin, Xue
Gong, Xue
Wu, Lele
Zhang, Jun
Liu, Weiguang
Li, Jian
Chen, Liming
author_facet Wang, Yuzhi
Lin, Xue
Gong, Xue
Wu, Lele
Zhang, Jun
Liu, Weiguang
Li, Jian
Chen, Liming
author_sort Wang, Yuzhi
collection PubMed
description Transcriptional repressor GATA binding 1 (TRPS1), an atypical GATA transcription factor, functions as a transcriptional repressor and is also implicated in human cancers. However, the underlying mechanism of TRPS1 contributing to malignancy remains obscure. In the current study, we report that TRPS1 recognizes both gene proximal and distal transcription start site (TSS) sequences to repress gene expression. Co-IP mass spectrometry and biochemical studies showed that TRPS1 binds to CHD4/NuRD(MTA2). Genome-wide and molecular studies revealed that CHD4/NuRD(MTA2) is required for TRPS1 transcriptional repression. Mechanically, TRPS1 and CHD4/NuRD(MTA2) form precision-guided transcriptional repression machinery in which TRPS1 guides the machinery to specific target sites by recognizing GATA elements, and CHD4/NuRD(MTA2) represses the transcription of target genes. Furthermore, TP63 was identified and validated to be a direct target of TRPS1-CHD4/NuRD(MTA2) complex, which represses TP63 expression by involving decommission of TP63 enhancer in the described precision-guided manner, leading to a reduction of the ΔNp63 level and contributing to migration and invasion of cancer cells.
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spelling pubmed-62990952018-12-19 Atypical GATA transcription factor TRPS1 represses gene expression by recruiting CHD4/NuRD(MTA2) and suppresses cell migration and invasion by repressing TP63 expression Wang, Yuzhi Lin, Xue Gong, Xue Wu, Lele Zhang, Jun Liu, Weiguang Li, Jian Chen, Liming Oncogenesis Article Transcriptional repressor GATA binding 1 (TRPS1), an atypical GATA transcription factor, functions as a transcriptional repressor and is also implicated in human cancers. However, the underlying mechanism of TRPS1 contributing to malignancy remains obscure. In the current study, we report that TRPS1 recognizes both gene proximal and distal transcription start site (TSS) sequences to repress gene expression. Co-IP mass spectrometry and biochemical studies showed that TRPS1 binds to CHD4/NuRD(MTA2). Genome-wide and molecular studies revealed that CHD4/NuRD(MTA2) is required for TRPS1 transcriptional repression. Mechanically, TRPS1 and CHD4/NuRD(MTA2) form precision-guided transcriptional repression machinery in which TRPS1 guides the machinery to specific target sites by recognizing GATA elements, and CHD4/NuRD(MTA2) represses the transcription of target genes. Furthermore, TP63 was identified and validated to be a direct target of TRPS1-CHD4/NuRD(MTA2) complex, which represses TP63 expression by involving decommission of TP63 enhancer in the described precision-guided manner, leading to a reduction of the ΔNp63 level and contributing to migration and invasion of cancer cells. Nature Publishing Group UK 2018-12-19 /pmc/articles/PMC6299095/ /pubmed/30563971 http://dx.doi.org/10.1038/s41389-018-0108-9 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wang, Yuzhi
Lin, Xue
Gong, Xue
Wu, Lele
Zhang, Jun
Liu, Weiguang
Li, Jian
Chen, Liming
Atypical GATA transcription factor TRPS1 represses gene expression by recruiting CHD4/NuRD(MTA2) and suppresses cell migration and invasion by repressing TP63 expression
title Atypical GATA transcription factor TRPS1 represses gene expression by recruiting CHD4/NuRD(MTA2) and suppresses cell migration and invasion by repressing TP63 expression
title_full Atypical GATA transcription factor TRPS1 represses gene expression by recruiting CHD4/NuRD(MTA2) and suppresses cell migration and invasion by repressing TP63 expression
title_fullStr Atypical GATA transcription factor TRPS1 represses gene expression by recruiting CHD4/NuRD(MTA2) and suppresses cell migration and invasion by repressing TP63 expression
title_full_unstemmed Atypical GATA transcription factor TRPS1 represses gene expression by recruiting CHD4/NuRD(MTA2) and suppresses cell migration and invasion by repressing TP63 expression
title_short Atypical GATA transcription factor TRPS1 represses gene expression by recruiting CHD4/NuRD(MTA2) and suppresses cell migration and invasion by repressing TP63 expression
title_sort atypical gata transcription factor trps1 represses gene expression by recruiting chd4/nurd(mta2) and suppresses cell migration and invasion by repressing tp63 expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299095/
https://www.ncbi.nlm.nih.gov/pubmed/30563971
http://dx.doi.org/10.1038/s41389-018-0108-9
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