GATA-dependent regulatory switches establish atrioventricular canal specificity during heart development.
GATA-dependent regulatory switches establish atrioventricular canal specificity during heart development.
复制标题
DOI：
10.1038/ncomms4680
复制
发表时间：
2014-04-28
影响因子：
16.6
通讯作者：
Christoffels, Vincent M.
中科院分区：
文献类型：
--
作者：
Stefanovic, Sonia;Barnett, Phil;van Duijvenboden, Karel;Weber, David;Gessler, Manfred;Christoffels, Vincent M.
The embryonic vertebrate heart tube develops an atrioventricular canal that divides the atrial and ventricular chambers, forms atrioventricular conduction tissue and organizes valve development. Here we assess the transcriptional mechanism underlying this localized differentiation process. We show that atrioventricular canal-specific enhancers are GATA-binding site-dependent and act as switches that repress gene activity in the chambers. We find that atrioventricular canal-specific gene loci are enriched in H3K27ac, a marker of active enhancers, in atrioventricular canal tissue and depleted in H3K27ac in chamber tissue. In the atrioventricular canal, Gata4 activates the enhancers in synergy with Bmp2/Smad signalling, leading to H3K27 acetylation. In contrast, in chambers, Gata4 cooperates with pan-cardiac Hdac1 and Hdac2 and chamber-specific Hey1 and Hey2, leading to H3K27 deacetylation and repression. We conclude that atrioventricular canal-specific enhancers are platforms integrating cardiac transcription factors, broadly active histone modification enzymes and localized co-factors to drive atrioventricular canal-specific gene activity. The atrioventricular canal partitions the developing vertebrate heart. Here, the authors show that the cardiac transcription factor Gata4 together with histone modification enzymes and localized co-factors binds atrioventricular canal-specific enhancers, thereby repressing gene activity in the cardiac chambers.
登录
查看更多内容
影响因子：
2.5
作者：
Christoffels, VM;Hoogaars, WMH;Campione, M
通讯作者：
Campione, M
影响因子：
20.1
作者：
Fahed AC;Gelb BD;Seidman JG;Seidman CE
通讯作者：
Seidman CE
影响因子：
5.3
作者：
Chang, SR;McKinsey, TA;Olson, EN
通讯作者：
Olson, EN
影响因子：
4.8
作者：
Di Lisi, R;Millino, C;Ausoni, S
通讯作者：
Ausoni, S
影响因子：
10.8
作者：
Hoogaars, WMH;Tessari, A;Christoffels, VM
通讯作者：
Christoffels, VM