The ChAHP Complex Counteracts Chromatin Looping at CTCF Sites that Emerged from SINE Expansions in Mouse
The ChAHP Complex Counteracts Chromatin Looping at CTCF Sites that Emerged from SINE Expansions in Mouse
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DOI：
10.1016/j.cell.2019.08.007
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发表时间：
2019-09-05
期刊：
影响因子：
64.5
通讯作者：
Buhler, Marc
中科院分区：
文献类型：
--
作者：
Kaaij, Lucas J. T.;Mohn, Fabio;Buhler, Marc
CCCTC结合因子(CTCF)和粘附素是三维染色质组织中的关键分子。CTCF划分的拓扑相关结构域(TADS)在物种之间保存得很好，尽管在转座子介导的基序扩张后，全基因组的CTCF结合发生了很大的分歧。因此，CTCF共识基序对TADS的预测很差，额外的因素必须调节CTCF结合和随后TAD的形成。在这里，我们证明了ChAHP复合体(CHD4，ADNP，HP1)与CTCF竞争一组共同的结合基序。在ADNP基因敲除细胞中，在ChAHP正常结合的位置形成了新的绝缘区，而近端正则边界被削弱。这些数据表明，CTCF介导的环形成是由一个独特的锌指蛋白复合体调控的。值得注意的是，ChAHP结合的位点主要位于发散较少的正弦B2转座元件中。这意味着ChAHP通过缓冲通过正弦扩展出现的新的CTCF结合位点来维持进化上保守的空间染色质组织。
CCCTC-binding factor (CTCF) and cohesin are key players in three-dimensional chromatin organization. The topologically associating domains (TADs) demarcated by CTCF are remarkably well conserved between species, although genome-wide CTCF binding has diverged substantially following transposon-mediated motif expansions. Therefore, the CTCF consensus motif poorly predicts TADs, and additional factors must modulate CTCF binding and subsequent TAD formation. Here, we demonstrate that the ChAHP complex (CHD4, ADNP, HP1) competes with CTCF for a common set of binding motifs. In Adnp knockout cells, novel insulated regions are formed at sites normally bound by ChAHP, whereas proximal canonical boundaries are weakened. These data reveal that CTCF-mediated loop formation is modulated by a distinct zinc-finger protein complex. Strikingly, ChAHP-bound loci are mainly situated within less diverged SINE B2 transposable elements. This implicates ChAHP in maintenance of evolutionarily conserved spatial chromatin organization by buffering novel CTCF binding sites that emerged through SINE expansions.