The Cohesin Complex Is Necessary for Epidermal Progenitor Cell Function through Maintenance of Self-Renewal Genes.
The Cohesin Complex Is Necessary for Epidermal Progenitor Cell Function through Maintenance of Self-Renewal Genes.
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DOI：
10.1016/j.celrep.2017.09.003
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发表时间：
2017-09-26
期刊：
影响因子：
8.8
通讯作者：
Sen GL
中科院分区：
文献类型：
--
作者：
Noutsou M;Li J;Ling J;Jones J;Wang Y;Chen Y;Sen GL
成体干细胞和祖细胞对于补充由于损伤或正常周转而丢失的组织至关重要。这些细胞如何保持自我更新并维持它们所居住的组织是一个积极的研究领域。在这里，我们表明，cohesin复合物，这以前被牵连在调节染色体分离和基因表达，是必要的，以促进表皮干细胞和祖细胞通过细胞自主机制的自我更新。粘着蛋白结合与开放染色质相关的基因组位点，包括DNA酶I超敏位点、RNA聚合酶II和组蛋白标记如H3K27ac和H3K4me3。由于开放染色质结构的丧失和关键自我更新基因的表达，减少的粘附素表达导致自发的表皮分化。我们的研究结果表明，粘着蛋白在调节染色质结构，允许执行的干细胞和祖细胞基因表达程序的突出作用。
Adult stem and progenitor cells are critical to replenishing lost tissue due to injury or normal turnover. How these cells maintain self-renewal and sustain the tissue they populate is an area of active investigation. Here we show that the cohesin complex, which has previously been implicated in regulating chromosome segregation and gene expression, is necessary to promote epidermal stem and progenitor cell self-renewal through cell autonomous mechanisms. Cohesin binds to genomic sites associated with open chromatin including DNase I hypersensitivity sites, RNA polymerase II, and histone marks such as H3K27ac and H3K4me3. Reduced cohesin expression results in spontaneous epidermal differentiation due to loss of open chromatin structure and expression of key self-renewal genes. Our results demonstrate a prominent role for cohesin in modulating chromatin structure to allow for enforcement of a stem and progenitor cell gene expression program.
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