.png){kind=icon}
返回
GATA4 Regulates Developing Endocardium Through Interaction With ETS1
.png){kind=icon}
OA
AI
DOI：10.1161/CIRCRESAHA.120.318102.png)
.png){kind=icon}
原文求助.png){kind=icon}
分享.png){kind=icon}
收藏
摘要
En 中文
Background:The pioneer transcription factor (TF) GATA4 (GATA Binding Protein 4) is expressed in multiple cardiovascular lineages and is essential for heart development. GATA4 lineage-specific occupancy in the developing heart underlies its lineage specific activities. Here, we characterized GATA4 chromatin occupancy in cardiomyocyte and endocardial lineages, dissected mechanisms that control lineage specific occupancy, and analyzed GATA4 regulation of endocardial gene expression. Methods:We mapped GATA4 chromatin occupancy in cardiomyocyte and endocardial cells of embryonic day 12.5 (E12.5) mouse heart using lineage specific, Cre-activated biotinylation of GATA4. Regulation of GATA4 pioneering activity was studied in cell lines stably overexpressing GATA4. GATA4 regulation of endocardial gene expression was analyzed using single cell RNA sequencing and luciferase reporter assays. Results:Cardiomyocyte-selective and endothelial-selective GATA4 occupied genomic regions had features of lineage specific enhancers. Footprints within cardiomyocyte- and endothelial-selective GATA4 regions were enriched for NKX2-5 (NK2 homeobox 5) and ETS1 (ETS Proto-Oncogene 1) motifs, respectively, and both of these TFs interacted with GATA4 in co-immunoprecipitation assays. In stable NIH3T3 cell lines expressing GATA4 with or without NKX2-5 or ETS1, the partner TFs re-directed GATA4 pioneer binding and augmented its ability to open previously inaccessible regions, with ETS1 displaying greater potency as a pioneer partner than NKX2-5. Single-cell RNA sequencing of embryonic hearts with endothelial cell-specific Gata4 inactivation identified Gata4-regulated endocardial genes, which were adjacent to GATA4-bound, endothelial regions enriched for both GATA4 and ETS1 motifs. In reporter assays, GATA4 and ETS1 cooperatively stimulated endothelial cell enhancer activity. Conclusions:Lineage selective non-pioneer TFs NKX2-5 and ETS1 guide the activity of pioneer TF GATA4 to bind and open chromatin and create active enhancers and mechanistically link ETS1 interaction to GATA4 regulation of endocardial development.
Keyword:
animals
chromatin
gene expression
genomics
immunoprecipitation
期刊
IF:
16.2
论文数:
1.3W
被引数:
6.4W
机构
引用论文
分享收藏Viral Gastroenteritis Associated with Genogroup II Norovirus among U.S. Military Personnel in Turkey, 2009.png)
PLoS ONEOAAI
PLoS ONEIF0
OAAI分享收藏分享收藏ChIP-Seq identification of weakly conserved heart enhancers弱保守性心脏增强子的chip-seq鉴定NATURE GENETICS
OAAI
NATURE GENETICSIF31.8
OAAI分享收藏Dynamic GATA4 enhancers shape the chromatin landscape central to heart development and disease动态GATA4增强剂塑造了心脏发育和疾病中心的染色质景观NATURE COMMUNICATIONSOAAI
NATURE COMMUNICATIONSIF15.7
OAAI分享收藏
查看更多内容