Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction.
Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction.
复制标题
DOI：
10.1016/j.cell.2017.09.018
复制
发表时间：
2017-10-19
期刊：
影响因子：
64.5
通讯作者：
Jain R
中科院分区：
文献类型：
--
作者：
Poleshko A;Shah PP;Gupta M;Babu A;Morley MP;Manderfield LJ;Ifkovits JL;Calderon D;Aghajanian H;Sierra-Pagán JE;Sun Z;Wang Q;Li L;Dubois NC;Morrisey EE;Lazar MA;Smith CL;Epstein JA;Jain R
祖细胞通过谱系特异性基因的协调表达和复杂染色质构型的修饰分化成专门的细胞类型。我们证明，在心脏祖细胞谱系限制期间，组蛋白脱乙酰酶（Hdac3）在核层组织异染色质。心肌细胞的规格与外周异染色质的重组相关，并且与脱乙酰酶活性无关，Hdac3 将含有谱系相关基因的外周异染色质连接到核纤层。心脏祖细胞中 Hdac3 的缺失会从核周边释放基因组区域，导致心脏基因过早表达并分化为心肌细胞；相反，将 Hdac3 限制在核外围可以挽救缺乏 Hdac3 的祖细胞的肌生成。我们的结果表明，谱系特异性因子激活的基因组区域的可用性部分是通过动态染色质-核层相互作用来调节的，并且祖细胞响应分化信号的能力可能取决于响应基因位点远离核外围的协调运动。核结构在发育过程中提供了独特的基因调控层，通过染色质-核层相互作用介导的染色质可及性的变化来协调细胞命运的决定
Progenitor cells differentiate into specialized cell types through coordinated expression of lineage-specific genes and modification of complex chromatin configurations. We demonstrate that a histone deacetylase (Hdac3) organizes heterochromatin at the nuclear lamina during cardiac progenitor lineage restriction. Specification of cardiomyocytes is associated with reorganization of peripheral heterochromatin and, independent of deacetylase activity, Hdac3 tethers peripheral heterochromatin containing lineage-relevant genes to the nuclear lamina. Deletion of Hdac3 in cardiac progenitor cells releases genomic regions from the nuclear periphery, leading to precocious cardiac gene expression and differentiation into cardiomyocytes; in contrast, restricting Hdac3 to the nuclear periphery rescues myogenesis in progenitors otherwise lacking Hdac3. Our results suggest that availability of genomic regions for activation by lineage-specific factors is regulated in part through dynamic chromatin-nuclear lamina interactions and that competence of a progenitor cell to respond to differentiation signals may depend upon coordinated movement of responding gene loci away from the nuclear periphery. Nuclear architecture provides a distinct layer of gene regulation during development, coordinating cell fate determination through changes in chromatin accessibility that are mediated by chromatin-nuclear lamina interactions
登录
查看更多内容
影响因子：
14.9
作者：
Lund E;Oldenburg AR;Collas P
通讯作者：
Collas P
影响因子：
64.8
作者：
Guelen, Lars;Pagie, Ludo;van Steensel, Bas
通讯作者：
van Steensel, Bas
DOI：
10.1038/nrg2485
发表时间：
2009-01
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
Loh KM;Chen A;Koh PW;Deng TZ;Sinha R;Tsai JM;Barkal AA;Shen KY;Jain R;Morganti RM;Shyh-Chang N;Fernhoff NB;George BM;Wernig G;Salomon REA;Chen Z;Vogel H;Epstein JA;Kundaje A;Talbot WS;Beachy PA;Ang LT;Weissman IL
通讯作者：
Weissman IL
影响因子：
64.5
作者：
Kind, Jop;Pagie, Ludo;van Steensel, Bas
通讯作者：
van Steensel, Bas