Regulation of CTCF loop formation during pancreatic cell differentiation.
Regulation of CTCF loop formation during pancreatic cell differentiation.
复制标题
DOI：
10.1038/s41467-023-41964-6
复制
发表时间：
2023-10-09
影响因子：
16.6
通讯作者：
Corces, Victor G.
中科院分区：
文献类型：
--
作者：
Lyu, Xiaowen;Rowley, M. Jordan;Kulik, Michael J.;Dalton, Stephen;Corces, Victor G.
细胞分化过程中的转录重编程涉及将增强子靶向负责建立细胞命运的基因。为了了解CTCF介导的染色质组织对细胞谱系定型的贡献，我们分析了人胚胎干细胞分化为胰岛类器官期间的3D染色质结构。我们发现，CTCF环的形成和拆卸在不同阶段的分化过程中，无论是招聘CTCF到新的锚网站或使用预先存在的网站，以前没有参与环的形成。CTCF向基因组中新位点的募集涉及H3 K9 me 3到H3 K9 me 2的去甲基化、DNA的去甲基化、先锋因子的募集以及位于新CTCF位点侧翼的核小体的定位。不参与环形成的现有CTCF位点通过在新锚之间的位点建立含有NIPBL和YY 1的新粘附素加载位点而成为功能性环锚。在这两种情况下，新的CTCF环的形成导致增强子启动子相互作用的加强和邻近环锚的基因的转录增加。这些结果表明，CTCF和cohesin在细胞分化过程中控制基因表达的重要作用。在这里，作者表明，hESC分化为胰腺细胞涉及CTCF环的变化，通过改变先锋因子招募，组蛋白修饰和DNA甲基化，导致增强子-启动子相互作用和基因表达的变化。
Transcription reprogramming during cell differentiation involves targeting enhancers to genes responsible for establishment of cell fates. To understand the contribution of CTCF-mediated chromatin organization to cell lineage commitment, we analyzed 3D chromatin architecture during the differentiation of human embryonic stem cells into pancreatic islet organoids. We find that CTCF loops are formed and disassembled at different stages of the differentiation process by either recruitment of CTCF to new anchor sites or use of pre-existing sites not previously involved in loop formation. Recruitment of CTCF to new sites in the genome involves demethylation of H3K9me3 to H3K9me2, demethylation of DNA, recruitment of pioneer factors, and positioning of nucleosomes flanking the new CTCF sites. Existing CTCF sites not involved in loop formation become functional loop anchors via the establishment of new cohesin loading sites containing NIPBL and YY1 at sites between the new anchors. In both cases, formation of new CTCF loops leads to strengthening of enhancer promoter interactions and increased transcription of genes adjacent to loop anchors. These results suggest an important role for CTCF and cohesin in controlling gene expression during cell differentiation. Here the authors show that differentiation of hESCs into pancreatic cells involves changes in CTCF loops by alteration of pioneer factor recruitment, histone modifications, and DNA methylation, leading to changes in enhancer-promoter interactions and gene expression.
登录
查看更多内容
影响因子：
64.5
作者：
Haarhuis JHI;van der Weide RH;Blomen VA;Yáñez-Cuna JO;Amendola M;van Ruiten MS;Krijger PHL;Teunissen H;Medema RH;van Steensel B;Brummelkamp TR;de Wit E;Rowland BD
通讯作者：
Rowland BD
影响因子：
16.6
作者：
Greenwald, William W.;Chiou, Joshua;Gaulton, Kyle J.
通讯作者：
Gaulton, Kyle J.
影响因子：
9.3
作者：
Durand NC;Shamim MS;Machol I;Rao SS;Huntley MH;Lander ES;Aiden EL
通讯作者：
Aiden EL
影响因子：
64.5
作者：
Boija A;Klein IA;Sabari BR;Dall'Agnese A;Coffey EL;Zamudio AV;Li CH;Shrinivas K;Manteiga JC;Hannett NM;Abraham BJ;Afeyan LK;Guo YE;Rimel JK;Fant CB;Schuijers J;Lee TI;Taatjes DJ;Young RA
通讯作者：
Young RA
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