The chromatin remodeller ATRX facilitates diverse nuclear processes, in a stochastic manner, in both heterochromatin and euchromatin.
The chromatin remodeller ATRX facilitates diverse nuclear processes, in a stochastic manner, in both heterochromatin and euchromatin.
复制标题
DOI：
10.1038/s41467-022-31194-7
复制
发表时间：
2022-06-17
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
染色质重塑剂ATRX与组蛋白伴侣DAXX相互作用，以将组蛋白变体H3.3存款在核小体周转位点。已知ATRX结合基因组的重复异染色质区域，包括端粒、核糖体DNA和臂间重复，其中许多是推定的G-四链体形成序列（PQS）。在这些位点，ATRX在促进复制、染色质修饰和转录的广泛的核过程中起辅助作用。在这里，使用染色质免疫沉淀的改进协议，我们表明，ATRX也结合常染色质中的活性调控元件。ATRX中的突变导致与染色质可及性降低、组蛋白修饰、转录因子结合和H3.3在其通常结合的序列处的沉积相关的基因表达的扰动。在红系细胞中，α-珠蛋白表达下调是ATR-X综合征的标志，染色质可及性和基因表达的扰动仅发生在一部分细胞中。这一过程的随机性表明，ATRX作为一个一般的促进细胞特异性转录和表观遗传程序，无论是在异染色质和常染色质。染色质重塑复合物ATRX可以促进基因表达，例如通过结合G-四链体（G4）以防止它们对表达的负面影响。在这里，作者使用单细胞方法表明，只有从ATRX突变患者中分离的红系细胞亚群具有降低的染色质可及性和α珠蛋白表达，这表明了一个随机过程。
The chromatin remodeller ATRX interacts with the histone chaperone DAXX to deposit the histone variant H3.3 at sites of nucleosome turnover. ATRX is known to bind repetitive, heterochromatic regions of the genome including telomeres, ribosomal DNA and pericentric repeats, many of which are putative G-quadruplex forming sequences (PQS). At these sites ATRX plays an ancillary role in a wide range of nuclear processes facilitating replication, chromatin modification and transcription. Here, using an improved protocol for chromatin immunoprecipitation, we show that ATRX also binds active regulatory elements in euchromatin. Mutations in ATRX lead to perturbation of gene expression associated with a reduction in chromatin accessibility, histone modification, transcription factor binding and deposition of H3.3 at the sequences to which it normally binds. In erythroid cells where downregulation of α-globin expression is a hallmark of ATR-X syndrome, perturbation of chromatin accessibility and gene expression occurs in only a subset of cells. The stochastic nature of this process suggests that ATRX acts as a general facilitator of cell specific transcriptional and epigenetic programmes, both in heterochromatin and euchromatin. The chromatin remodeling complex ATRX can promote gene expression, for example by binding G-quadruplexes (G4s) to prevent their negative effect on expression. Here the authors use a single-cell approach to show that only a subset of erythroid cells isolated from patients with ATRX mutations have reduced chromatin accessibility and alpha globin expression, suggesting a stochastic process.
登录
查看更多内容
影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
16.8
作者：
Iwase, Shigeki;Xiang, Bin;Ghosh, Sharmistha;Ren, Ting;Lewis, Peter W.;Cochrane, Jesse C.;Allis, C. David;Picketts, David J.;Patel, Dinshaw J.;Li, Haitao;Shi, Yang
通讯作者：
Shi, Yang
影响因子：
64.5
作者：
Goldberg AD;Banaszynski LA;Noh KM;Lewis PW;Elsaesser SJ;Stadler S;Dewell S;Law M;Guo X;Li X;Wen D;Chapgier A;DeKelver RC;Miller JC;Lee YL;Boydston EA;Holmes MC;Gregory PD;Greally JM;Rafii S;Yang C;Scambler PJ;Garrick D;Gibbons RJ;Higgs DR;Cristea IM;Urnov FD;Zheng D;Allis CD
通讯作者：
Allis CD
影响因子：
12.3
作者：
Day DS;Luquette LJ;Park PJ;Kharchenko PV
通讯作者：
Kharchenko PV
影响因子：
3.7
作者：
Clynes D;Jelinska C;Xella B;Ayyub H;Taylor S;Mitson M;Bachrati CZ;Higgs DR;Gibbons RJ
通讯作者：
Gibbons RJ