The NuRD complex cooperates with SALL4 to orchestrate reprogramming.
The NuRD complex cooperates with SALL4 to orchestrate reprogramming.
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DOI：
10.1038/s41467-023-38543-0
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发表时间：
2023-05-18
影响因子：
16.6
通讯作者：
Pei, Duanqing
中科院分区：
文献类型：
--
作者：
Wang, Bo;Li, Chen;Ming, Jin;Wu, Linlin;Fang, Shicai;Huang, Yi;Lin, Lihui;Liu, He;Kuang, Junqi;Zhao, Chengchen;Huang, Xingnan;Feng, Huijian;Guo, Jing;Yang, Xuejie;Guo, Liman;Zhang, Xiaofei;Chen, Jiekai;Liu, Jing;Zhu, Ping;Pei, Duanqing
细胞命运决定涉及基因组的重新布线，但在染色质水平上仍然知之甚少。在这里，我们报道染色质重塑复合物 NuRD 参与体细胞重编程早期阶段开放染色质的关闭。 Sall4、Jdp2、Glis1 和 Esrrb 可以有效地将 MEF 重编程为 iPSC，但只有 Sall4 才能招募 NuRD 的内源成分。然而，与通过突变或删除 N 末端 NuRD 相互作用基序来破坏已知的 Sall4-NuRD 相互作用（使 Sall4 无法重编程）相比，敲除 NuRD 组件只能适度减少重编程。值得注意的是，通过将 NuRD 相互作用基序移植到 Jdp2 上可以部分修复这些缺陷。对染色质可及性动力学的进一步分析表明，Sall4-NuRD 轴在重编程早期阶段关闭开放染色质中发挥着关键作用。 Sall4-NuRD 封闭的染色质位点编码抗重编程基因。这些结果确定了 NuRD 在重编程中以前未被认识的作用，并可能进一步阐明染色质闭合是细胞命运控制的关键步骤。体细胞重编程涉及转录和表观遗传重置，但我们尚未完全了解这个过程。在这里，他们表明 Jdp2、Glis1、Esrrb 和 Sall4 可以通过招募 NuRD 复合物来封闭染色质来介导重编程，这突显了其在细胞命运控制中的潜在作用。
Cell fate decision involves rewiring of the genome, but remains poorly understood at the chromatin level. Here, we report that chromatin remodeling complex NuRD participates in closing open chromatin in the early phase of somatic reprogramming. Sall4, Jdp2, Glis1 and Esrrb can reprogram MEFs to iPSCs efficiently, but only Sall4 is indispensable capable of recruiting endogenous components of NuRD. Yet knocking down NuRD components only reduces reprogramming modestly, in contrast to disrupting the known Sall4-NuRD interaction by mutating or deleting the NuRD interacting motif at its N-terminus that renders Sall4 inept to reprogram. Remarkably, these defects can be partially rescured by grafting NuRD interacting motif onto Jdp2. Further analysis of chromatin accessibility dynamics demonstrates that the Sall4-NuRD axis plays a critical role in closing the open chromatin in the early phase of reprogramming. Among the chromatin loci closed by Sall4-NuRD encode genes resistant to reprogramming. These results identify a previously unrecognized role of NuRD in reprogramming, and may further illuminate chromatin closing as a critical step in cell fate control. Somatic reprogramming involves both transcriptional and epigenetic resetting, but we don’t yet fully understand this process. Here they show that Jdp2, Glis1, Esrrb, and Sall4 can mediate reprogramming by recruiting the NuRD complex to close chromatin, highlighting a potential role in cell fate control.
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重编程因子表达引发了广泛的靶向染色质重塑。
影响因子：
23.9
作者：
Koche RP;Smith ZD;Adli M;Gu H;Ku M;Gnirke A;Bernstein BE;Meissner A
通讯作者：
Meissner A
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
23.9
作者：
Buganim, Yosef;Markoulaki, Styliani;van Wietmarschen, Niek;Hoke, Heather;Wu, Tao;Ganz, Kibibi;Akhtar-Zaidi, Batool;He, Yupeng;Abraham, Brian J.;Porubsky, David;Kulenkampff, Elisabeth;Faddah, Dina A.;Shi, Linyu;Gao, Qing;Sarkar, Sovan;Cohen, Malkiel;Goldmann, Johanna;Nery, Joseph R.;Schultz, Matthew D.;Ecker, Joseph R.;Xiao, Andrew;Young, Richard A.;Lansdorp, Peter M.;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
影响因子：
2.3
作者：
Jaffer S;Goh P;Abbasian M;Nathwani AC
通讯作者：
Nathwani AC
影响因子：
23.9
作者：
Abernathy DG;Kim WK;McCoy MJ;Lake AM;Ouwenga R;Lee SW;Xing X;Li D;Lee HJ;Heuckeroth RO;Dougherty JD;Wang T;Yoo AS
通讯作者：
Yoo AS