Baf60c is a nuclear Notch signaling component required for the establishment of left-right asymmetry

Baf60c is a nuclear Notch signaling component required for the establishment of left-right asymmetry
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DOI:
10.1073/pnas.0608118104
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发表时间:
2007-01-16
影响因子:
11.1
通讯作者:
Bruneau, Benoit G.
Bruneau, Benoit G.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Takeuchi, Jun K.;Lickert, Heiko;Bruneau, Benoit G.

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Notch介导的Nodal在脊椎动物淋巴结的诱导是启动左右(LR)不对称的关键步骤。在小鼠和斑马鱼中,我们发现Baf 60 c,Swi/Snf样BAF染色质重塑复合物的亚基,是建立LR不对称性所必需的。Baf 60 c敲除小鼠胚胎不能在节点处激活Nodal,并且还具有异常的节点形态,其中冠细胞和窝细胞混合。在细胞培养中,Baf 60 c是Notch依赖性转录激活所必需的,并具有稳定活化的Notch及其DNA结合伴侣RBP-J之间相互作用的功能。Brg 1也是这些过程所必需的,这表明BAF复合物是核Notch信号传导的关键组分。我们提出Baf 60 c在Notch依赖的转录和LR不对称性中的关键作用。
Notch-mediated induction of Nodal at the vertebrate node is a critical step in initiating left-right (LR) asymmetry. In mice and zebrafish we show that Baf60c, a subunit of the Swi/Snf-like BAF chromatin remodeling complex, is essential for establishment of LR asymmetry. Baf60c knockdown mouse embryos fail to activate Nodal at the node and also have abnormal node morphology with mixing of crown and pit cells. In cell culture, Baf60c is required for Notch-dependent transcriptional activation and functions to stabilize interactions between activated Notch and its DNA-binding partner, RBP-J. Brg1 is also required for these processes, suggesting that BAF complexes are key components of nuclear Notch signaling. We propose a critical role for Baf60c in Notch-dependent transcription and LR asymmetry.