A Transcription Factor Collective Defines Cardiac Cell Fate and Reflects Lineage History
A Transcription Factor Collective Defines Cardiac Cell Fate and Reflects Lineage History
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DOI：
10.1016/j.cell.2012.01.030
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发表时间：
2012-02-03
期刊：
影响因子：
64.5
通讯作者：
Furlong, Eileen E. M.
中科院分区：
文献类型：
--
作者：
Junion, Guillaume;Spivakov, Mikhail;Furlong, Eileen E. M.
细胞命运的决定是通过整合诱导信号和组织特异性转录因子（TF）驱动的，尽管关于这些信息如何在顺式中收敛的细节仍不清楚。在这里，我们证明了果蝇心脏规格，包括Wg和Dpp信号的效应器，作为一个集体单位，以合作调节心脏增强子的活性，在体内和体外的五个遗传组件。它们的组合结合不需要任何特定的基序方向或间距，这表明增强子功能的另一种模式，其中合作活性与广泛的基序灵活性一起发生。一小部分的增强子共同占据的心源性TF在相邻的内脏中胚层有意想不到的活动，但可以通过单位点突变，使心脏活跃。考虑到心脏和内脏细胞都来自背侧中胚层，这种“休眠”TF结合特征可能代表了这些细胞发育谱系的分子足迹。
Cell fate decisions are driven through the integration of inductive signals and tissue-specific transcription factors (TFs), although the details on how this information converges in cis remain unclear. Here, we demonstrate that the five genetic components essential for cardiac specification in Drosophila, including the effectors of Wg and Dpp signaling, act as a collective unit to cooperatively regulate heart enhancer activity, both in vivo and in vitro. Their combinatorial binding does not require any specific motif orientation or spacing, suggesting an alternative mode of enhancer function whereby cooperative activity occurs with extensive motif flexibility. A fraction of enhancers co-occupied by cardiogenic TFs had unexpected activity in the neighboring visceral mesoderm but could be rendered active in heart through single-site mutations. Given that cardiac and visceral cells are both derived from the dorsal mesoderm, this "dormant'' TF binding signature may represent a molecular footprint of these cells' developmental lineage.