Transformation of Accessible Chromatin and 3D Nucleome Underlies Lineage Commitment of Early T Cells.
Transformation of Accessible Chromatin and 3D Nucleome Underlies Lineage Commitment of Early T Cells.
复制标题
DOI：
10.1016/j.immuni.2018.01.013
复制
发表时间：
2018-02-20
期刊：
影响因子：
32.4
通讯作者：
Zhao K
中科院分区：
文献类型：
--
作者：
Hu G;Cui K;Fang D;Hirose S;Wang X;Wangsa D;Jin W;Ried T;Liu P;Zhu J;Rothenberg EV;Zhao K
染色质重组如何协调从造血干/祖细胞（HSPC）到成熟免疫细胞的分化和谱系定型尚未得到很好的理解。在这里，我们进行了一个综合分析的染色质可及性，拓扑相关结构域，AB区室，和基因表达从HSPC到CD4 + CD8+双阳性T细胞。我们发现，在从双阴性阶段2（DN2）到DN3的过渡过程中，伴随着T谱系定型，染色质组织的所有三个水平都发生了突然的全基因组变化。转录因子BCL11B是T细胞定型的关键调节因子，与染色质相互作用的增加有关，而Bcl11b的缺失会损害其靶基因处的染色质相互作用。我们认为，这些大规模的和协调一致的染色质组织的变化为细胞提供了一个能量屏障，以扭转其命运的早期阶段或重定向到替代品，从而锁定细胞的命运到T谱系。细胞分化和细胞命运选择涉及大量的染色质重组。通过对调节组、3D核组和转录组的综合分析，Hu和Cui等人揭示了在DN2-到-DN3转变时调节组和3D核组的突然全局变化，建立了染色质屏障以将细胞命运锁定到T谱系中。
How chromatin reorganization coordinates differentiation and lineage commitment from hematopoietic stem/progenitor cells (HSPC) to mature immune cells has not been well understood. Here, we carried out an integrative analysis of chromatin accessibility, topologically associating domains, AB compartments, and gene expression from HSPC to CD4+CD8+ double positive T cells. We found that abrupt genome-wide changes at all three levels of chromatin organization occur during the transition from double negative stage 2 (DN2) to DN3, accompanying the T lineage commitment. The transcription factor BCL11B, a critical regulator of T cell commitment, is associated with increased chromatin interaction and Bcl11b deletion compromised chromatin interaction at its target genes. We propose that these large-scale and concerted changes in chromatin organization present an energy barrier for the cell to reverse its fate to earlier stages or to redirect to alternatives, thus locking the cell fate into the T lineages. Cellular differentiation and cell fate choice involve substantial chromatin reorganization. Through an integrative analysis of regulome, 3D nucleome and transcriptome, Hu and Cui et al. uncover abrupt global changes in regulome and 3D nucleome at the DN2-to-DN3 transition, establishing a chromatin barrier to lock cell fate into the T lineages.
登录
查看更多内容
DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
3.7
作者：
Ariki R;Morikawa S;Mabuchi Y;Suzuki S;Nakatake M;Yoshioka K;Hidano S;Nakauchi H;Matsuzaki Y;Nakamura T;Goitsuka R
通讯作者：
Goitsuka R
哺乳动物SWI/SNF复合物的蛋白质组学和生物信息学分析确定了在人类恶性肿瘤中的广泛作用。
影响因子：
30.8
作者：
Kadoch, Cigall;Hargreaves, Diana C.;Hodges, Courtney;Elias, Laura;Ho, Lena;Ranish, Jeff;Crabtree, Gerald R.
通讯作者：
Crabtree, Gerald R.
影响因子：
10.5
作者：
Denker A;de Laat W
通讯作者：
de Laat W
影响因子：
3.5
作者：
Dekker J;Heard E
通讯作者：
Heard E