HAND2 targets define a network of transcriptional regulators that compartmentalize the early limb bud mesenchyme.
HAND2 targets define a network of transcriptional regulators that compartmentalize the early limb bud mesenchyme.
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DOI：
10.1016/j.devcel.2014.09.018
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发表时间：
2014-11-10
影响因子：
11.8
通讯作者：
Zeller, Rolf
中科院分区：
文献类型：
--
作者：
Osterwalder, Marco;Speziale, Dario;Shoukry, Malak;Mohan, Rajiv;Ivanek, Robert;Kohler, Manuel;Beisel, Christian;Wen, Xiaohui;Scales, Suzie J.;Christoffels, Vincent M.;Visel, Axel;Lopez-Rios, Javier;Zeller, Rolf
控制脊椎动物发育的遗传网络已经得到了很好的研究，但反式作用因子与顺式调控模块(CRM)的相互作用如何整合到基因表达的时空调控中还不清楚。转录调控因子HAND2在肢体、心脏和颧弓发育过程中是必需的。在这里，我们从小鼠胚胎和肢芽中鉴定了富含HAND2染色质复合体的基因组区域。然后，我们分析了基因组中编码早期肢芽所需转录调控因子的HAND2靶标CRM。HAND2通过影响Gli3和Tbx3的表达，控制近端肢芽功能基因的表达，并协调新生肢芽间充质的前后极性的建立。Tbx3需要在HAND2下游完善后Gli3表达边界。我们的分析揭示了在HAND2下游和SHH信号上游建立不同的间充质区段的转录电路。
The genetic networks that govern vertebrate development are well studied, but how the interactions of trans-acting factors with cis-regulatory modules (CRMs) are integrated into spatio-temporal regulation of gene expression is not clear. The transcriptional regulator HAND2 is required during limb, heart and branchial arch development. Here, we identify the genomic regions enriched in HAND2 chromatin complexes from mouse embryos and limb buds. Then, we analyze the HAND2 target CRMs in the genomic landscapes encoding transcriptional regulators required in early limb buds. HAND2 controls the expression of genes functioning in the proximal limb bud and orchestrates the establishment of anterior and posterior polarity of the nascent limb bud mesenchyme by impacting on Gli3 and Tbx3 expression. TBX3 is required downstream of HAND2 to refine the posterior Gli3 expression boundary. Our analysis uncovers the transcriptional circuits that function in establishing distinct mesenchymal compartments downstream of HAND2 and upstream of SHH signaling.
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影响因子：
11.8
作者：
Lopez-Rios, Javier;Speziale, Dario;Robay, Dimitri;Scotti, Martina;Osterwalder, Marco;Nusspaumer, Gretel;Galli, Antonella;Hollaender, Georg A.;Kmita, Marie;Zeller, Rolf
通讯作者：
Zeller, Rolf
影响因子：
11.8
作者：
Li, Danyi;Sakuma, Rui;Hui, Chi-chung
通讯作者：
Hui, Chi-chung
影响因子：
2.7
作者：
Chiang, C;Litingtung, Y;Fallon, JF
通讯作者：
Fallon, JF
影响因子：
16
作者：
Capdevila, J;Tsukui, T;Belmonte, JCI
通讯作者：
Belmonte, JCI
影响因子：
4.6
作者：
Capellini, Terence D.;Vaccari, Giulia;Zappavigna, Vincenzo
通讯作者：
Zappavigna, Vincenzo