Chromatin in embryonic stem cell neuronal diiferentiation
作者单位:National Cancer Institute National Institutes of Health Bethesda MD 20892 USA
会议名称:《第十五届国际药理学大会》
会议日期:2006年
学科分类:1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 10[医学]
摘 要:正 Embryonic stem (ES) cells, derived from the inner cell mass of the blastocyst. are unique in their ability to both self-renew and to differentiate into the three germ layers. Here we show global changes in nuclear architecture and chromatin structure during ES cell neuronal differentiation. A hyperdynamic pool of chromatin proteins is loosely bound in ES cells and become tightly associated with chromatin in neuronal progenitor cells (NPCs). The levels of activity-associated histone marks, such as acetylated histones H3 and H4. are reduced during neuronal differentiation, while H3-triMeK9 is increased. Moreover, genomic tiling arrays, uridine incorporation assays and RT-PCR experiments revealed higher global transcriptional activity in ES cells compared with ES-derived NPCs and neurons. Taken together, these results suggest that chromatin is a fundamental regulator of neuronal commitment and that gene silencing by chromatin condensation and heterochromatin formation promotes neuronal differentiation.