Cooperative binding of AP-1 and TEAD4 modulates the balance between vascular smooth muscle and hemogenic cell fate.
Cooperative binding of AP-1 and TEAD4 modulates the balance between vascular smooth muscle and hemogenic cell fate.
复制标题
DOI：
10.1242/dev.139857
复制
发表时间：
2016-12-01
期刊：
影响因子：
--
通讯作者：
Bonifer C
中科院分区：
文献类型：
--
作者：
Obier N;Cauchy P;Assi SA;Gilmour J;Lie-A-Ling M;Lichtinger M;Hoogenkamp M;Noailles L;Cockerill PN;Lacaud G;Kouskoff V;Bonifer C
细胞外信号进入细胞核的传输涉及诱导型转录因子，但不同的信号通路如何以细胞类型特异性的方式起作用还知之甚少。在这里，我们研究了AP-1转录因子家族在血液发育中的调节作用，使用胚胎干细胞分化加上全基因组转录因子结合和基因表达分析。AP-1因子响应MAP激酶信号传导，并包含FOS、ATF和JUN蛋白的二聚体。为了研究AP-1调控的基因，并研究它如何与其他诱导型转录因子相互作用，我们使用显性负性FOS肽废除了其全局DNA结合活性。我们发现，FOS和JUN结合并激活一组特定的血管基因，AP-1抑制剂将平滑肌和造血分化之间的平衡向血液转移。此外，AP-1是TEAD 4从头结合所必需的，TEAD 4是一种与Hippo信号传导相关的转录因子。我们自下而上的方法表明，AP-1和TEAD 4相关的顺式调控元件形成枢纽的多个信号响应转录因子，并定义顺式组，调节血管和造血发育的外部信号。 AP-1激活生血内皮细胞中血管基因的表达，并且是Hippo信号传导转录因子TEAD 4从头结合所需的。
The transmission of extracellular signals into the nucleus involves inducible transcription factors, but how different signalling pathways act in a cell type-specific fashion is poorly understood. Here, we studied the regulatory role of the AP-1 transcription factor family in blood development using embryonic stem cell differentiation coupled with genome-wide transcription factor binding and gene expression analyses. AP-1 factors respond to MAP kinase signalling and comprise dimers of FOS, ATF and JUN proteins. To examine genes regulated by AP-1 and to examine how it interacts with other inducible transcription factors, we abrogated its global DNA-binding activity using a dominant-negative FOS peptide. We show that FOS and JUN bind to and activate a specific set of vascular genes and that AP-1 inhibition shifts the balance between smooth muscle and hematopoietic differentiation towards blood. Furthermore, AP-1 is required for de novo binding of TEAD4, a transcription factor connected to Hippo signalling. Our bottom-up approach demonstrates that AP-1- and TEAD4-associated cis-regulatory elements form hubs for multiple signalling-responsive transcription factors and define the cistrome that regulates vascular and hematopoietic development by extrinsic signals. AP-1 activates the expression of vascular genes in hemogenic endothelial cells and is required for de novo binding of the Hippo signaling transcription factor TEAD4.
登录
查看更多内容
影响因子：
4
作者：
Hess, J;Angel, P;Schorpp-Kistner, M
通讯作者：
Schorpp-Kistner, M
影响因子：
11.8
作者：
Goode DK;Obier N;Vijayabaskar MS;Lie-A-Ling M;Lilly AJ;Hannah R;Lichtinger M;Batta K;Florkowska M;Patel R;Challinor M;Wallace K;Gilmour J;Assi SA;Cauchy P;Hoogenkamp M;Westhead DR;Lacaud G;Kouskoff V;Göttgens B;Bonifer C
通讯作者：
Bonifer C
影响因子：
64.8
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
通讯作者：
Speck, Nancy A.
影响因子：
11.4
作者：
Calero-Nieto, Fernando J.;Ng, Felicia S.;Wilson, Nicola K.;Hannah, Rebecca;Moignard, Victoria;Leal-Cervantes, Ana I.;Jimenez-Madrid, Isabel;Diamanti, Evangelia;Wernisch, Lorenz;Goettgens, Berthold
通讯作者：
Goettgens, Berthold
DOI：
10.1242/dev.106054
发表时间：
2014-06
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Gilmour J;Assi SA;Jaegle U;Kulu D;van de Werken H;Clarke D;Westhead DR;Philipsen S;Bonifer C
通讯作者：
Bonifer C