Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation.
Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation.
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DOI：
10.1038/s41467-021-23610-1
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发表时间：
2021-06-09
影响因子：
16.6
通讯作者：
Payer B
中科院分区：
文献类型：
--
作者：
Bauer M;Vidal E;Zorita E;Üresin N;Pinter SF;Filion GJ;Payer B
染色体组织的一个标志是分为转录活性A区室和受抑制的B区室，以及拓扑关联结构域（TADs）。这两种结构都被认为是不存在于失活的小鼠X染色体，但在X-再激活期间通过转录再激活和染色质开放重新建立。在这里，我们结合联合收割机定制的小鼠iPSC重编程系统和高分辨率Hi-C，以产生在X-重激活期间结合基因重激活、染色质开放和染色体拓扑结构的时间过程。与以前的观察结果相反，我们观察到A/B样车厢上的不活跃的X窝藏多个子车厢。虽然部分X-再激活起始于富含X-失活逃逸物的隔室内，但随后它沿染色体迅速沿着Xist的下调。重要的是，我们发现，转录前的转录和启动Xist穷人隔间。在这里，我们表明，在X-激活，同时建立Xist作为一个共同的分母，转录形成和转录激活是因果独立的。认为A/B区室和TADs都不存在于失活的X染色体中，但在X-再活化期间随着转录再活化和染色质开放而重新建立。在这里，作者在X-再激活过程中观察到了基因再激活、染色质开放和染色体拓扑结构，在X-再激活过程中观察到了非活性X上的A/B样区室，这些区室独立于转录指导了X-再激活过程中的染色体形成。
A hallmark of chromosome organization is the partition into transcriptionally active A and repressed B compartments, and into topologically associating domains (TADs). Both structures were regarded to be absent from the inactive mouse X chromosome, but to be re-established with transcriptional reactivation and chromatin opening during X-reactivation. Here, we combine a tailor-made mouse iPSC reprogramming system and high-resolution Hi-C to produce a time course combining gene reactivation, chromatin opening and chromosome topology during X-reactivation. Contrary to previous observations, we observe A/B-like compartments on the inactive X harbouring multiple subcompartments. While partial X-reactivation initiates within a compartment rich in X-inactivation escapees, it then occurs rapidly along the chromosome, concomitant with downregulation of Xist. Importantly, we find that TAD formation precedes transcription and initiates from Xist-poor compartments. Here, we show that TAD formation and transcriptional reactivation are causally independent during X-reactivation while establishing Xist as a common denominator. Both A/B compartments and TADs are thought to be absent from the inactive X chromosome, but to be re-established with transcriptional reactivation and chromatin opening during X-reactivation. Here, the authors characterise gene reactivation, chromatin opening and chromosome topology during X-reactivation, observe A/B-like compartments on the inactive X that guide TAD formation independently of transcription during X-reactivation.
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DOI：
10.1126/science.aal2512
发表时间：
2017-06-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Almeida M;Pintacuda G;Masui O;Koseki Y;Gdula M;Cerase A;Brown D;Mould A;Innocent C;Nakayama M;Schermelleh L;Nesterova TB;Koseki H;Brockdorff N
通讯作者：
Brockdorff N
DOI：
10.1073/pnas.0408021101
发表时间：
2004-12-14
影响因子：
11.1
作者：
Chadwick, BP;Willard, HF
通讯作者：
Willard, HF
影响因子：
3.7
作者：
de Napoles, Mariana;Nesterova, Tatyana;Brockdorff, Neil
通讯作者：
Brockdorff, Neil
影响因子：
3.7
作者：
Abranches E;Silva M;Pradier L;Schulz H;Hummel O;Henrique D;Bekman E
通讯作者：
Bekman E
影响因子：
64.5
作者：
Bonev B;Mendelson Cohen N;Szabo Q;Fritsch L;Papadopoulos GL;Lubling Y;Xu X;Lv X;Hugnot JP;Tanay A;Cavalli G
通讯作者：
Cavalli G