Francis Nicole J, Follmer Nicole E, Simon Matthew D, Aghia George, Butler Jeffrey D
Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.
Cell. 2009 Apr 3;137(1):110-22. doi: 10.1016/j.cell.2009.02.017. Epub 2009 Mar 19.
The transcriptional status of a gene can be maintained through multiple rounds of cell division during development. This epigenetic effect is believed to reflect heritable changes in chromatin folding and histone modifications or variants at target genes, but little is known about how these chromatin features are inherited through cell division. A particular challenge for maintaining transcription states is DNA replication, which disrupts or dilutes chromatin-associated proteins and histone modifications. PRC1-class Polycomb group protein complexes are essential for development and are thought to heritably silence transcription by altering chromatin folding and histone modifications. It is not known whether these complexes and their effects are maintained during DNA replication or subsequently re-established. We find that when PRC1-class Polycomb complex-bound chromatin or DNA is replicated in vitro, Polycomb complexes remain bound to replicated templates. Retention of Polycomb proteins through DNA replication may contribute to maintenance of transcriptional silencing through cell division.
在发育过程中,基因的转录状态可通过多轮细胞分裂得以维持。这种表观遗传效应被认为反映了靶基因处染色质折叠以及组蛋白修饰或变体的可遗传变化,但对于这些染色质特征如何通过细胞分裂遗传却知之甚少。维持转录状态的一个特殊挑战是DNA复制,它会破坏或稀释与染色质相关的蛋白质和组蛋白修饰。PRC1类多梳蛋白复合体对发育至关重要,并且被认为通过改变染色质折叠和组蛋白修饰来遗传性地使转录沉默。目前尚不清楚这些复合体及其效应在DNA复制过程中是得以维持还是随后重新建立。我们发现,当PRC1类多梳复合体结合的染色质或DNA在体外进行复制时,多梳复合体仍与复制后的模板结合。通过DNA复制保留多梳蛋白可能有助于通过细胞分裂维持转录沉默。