Chromatin remodeling during mouse and human embryonic stem cell differentiation
Chromatin remodeling during mouse and human embryonic stem cell differentiation
复制标题
DOI：
10.1002/dvdy.21545
复制
发表时间：
2008-05-01
影响因子：
2.5
通讯作者：
Murry, Charles E.
中科院分区：
文献类型：
--
作者：
Golob, Jonathan L.;Paige, Sharon L.;Murry, Charles E.
胚胎干细胞（ESC）分化是研究发育调控位点染色质变化的一个很好的模型。分化小鼠和人类ESC增加组蛋白H3上赖氨酸9的全基因组乙酰化（常染色质）和三甲基化（异染色质）。Oct4基因座在未分化的ESC中表达时是常染的，在分化后是异染的。中胚层特异性转录因子Brachyury T尚未在未分化细胞中表达，其中其基因座具有“二价”三甲基赖氨酸4和赖氨酸27修饰。在定向分化为心前中胚层期间，激活的短尾畸形基因座具有高水平的三甲基赖氨酸4（常染色质），在基因沉默后切换为异染色质。因此，ESC分化伴随着全基因组对常染色质或异染色质的承诺。未分化的人胚胎干细胞biopsy修改brachyury基因座，在中胚层诱导过程中将其激活为常染色质，随后将其抑制为异染色质，据我们所知，这表明了对中胚层和内胚层分化所必需的基因座处的染色质动力学的首次分析。
Embryonic stem cell (ESC) differentiation is an excellent model to study chromatin changes at developmentally regulated loci. Differentiating mouse and human ESCs increase genome-wide acetylation (euchromatic) and tri-methylation (heterochromatic) of lysine 9 on histone H3. The Oct4 locus is euchromatic when expressed in undifferentiated ESCs and heterochromatic after differentiation. Brachyury T, a mesoderm-specific transcription factor, is not yet expressed in undifferentiated cells, where its locus has "bivalent" tri-methyl lysine 4 and lysine 27 modifications. During directed differentiation to pre-cardiac mesoderm, the activated brachyury locus has high levels of tri-methyl lysine 4 (euchromatin), switching to heterochromatin after gene silencing. Thus, ESC differentiation is accompanied by genome-wide commitment to euchromatin or heterochromatin. Undifferentiated hESCs bivalently modify the brachyury locus, activate it to euchromatin during mesoderm induction, and subsequently repress it to heterochromatin, demonstrating, to our knowledge, the first analysis of chromatin dynamics at a locus essential for mesoderm and endoderm differentiation.