2017年9月1日
ZNF281 enhances cardiac reprogramming by modulating cardiac and inflammatory gene expression.
Genes & development
- 巻
- 31
- 号
- 17
- 開始ページ
- 1770
- 終了ページ
- 1783
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1101/gad.305482.117
- 出版者・発行元
- COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
Direct reprogramming of fibroblasts to cardiomyocytes represents a potential means of restoring cardiac function following myocardial injury. AKT1 in the presence of four cardiogenic transcription factors, GATA4, HAND2, MEF2C, and TBX5 (AGHMT), efficiently induces the cardiac gene program in mouse embryonic fibroblasts but not adult fibroblasts. To identify additional regulators of adult cardiac reprogramming, we performed an unbiased screen of transcription factors and cytokines for those that might enhance or suppress the cardiogenic activity of AGHMT in adult mouse fibroblasts. Among a collection of inducers and repressors of cardiac reprogramming, we discovered that the zinc finger transcription factor 281 (ZNF281) potently stimulates cardiac reprogramming by genome-wide association with GATA4 on cardiac enhancers. Concomitantly, ZNF281 suppresses expression of genes associated with inflammatory signaling, suggesting the antagonistic convergence of cardiac and inflammatory transcriptional programs. Consistent with an inhibitory influence of inflammatory pathways on cardiac reprogramming, blockade of these pathways with anti-inflammatory drugs or components of the nucleosome remodeling deacetylase (NuRD) complex, which associate with ZNF281, stimulates cardiac gene expression. We conclude that ZNF281 acts at a nexus of cardiac and inflammatory gene programs, which exert opposing influences on fibroblast to cardiac reprogramming.
- リンク情報
-
- DOI
- https://doi.org/10.1101/gad.305482.117
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/28982760
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666675
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000412275500006&DestApp=WOS_CPL
- ID情報
-
- DOI : 10.1101/gad.305482.117
- ISSN : 0890-9369
- eISSN : 1549-5477
- PubMed ID : 28982760
- PubMed Central 記事ID : PMC5666675
- Web of Science ID : WOS:000412275500006