Abstract:
DNA replication produces a global disorganization of chromatin structure that takes hours to be restored. However, how these chromatin rearrangements affect the regulation of gene expression and the maintenance of cell identity is not clear. Here, we use ChOR-seq and ChrRNA-seq experiments to analyze RNA polymerase II (RNAPII) activity and nascent RNA synthesis during the first hours after chromatin replication in human cells. We observe that transcription elongation is rapidly reactivated in nascent chromatin but that RNAPII abundance and distribution are altered, producing heterogeneous changes in RNA synthesis. Moreover, this first wave of transcription results in RNAPII blockages behind the replication fork, leading to changes in alternative splicing. Altogether, our results deepen our understanding of how transcriptional programs are regulated during cell division and uncover molecular mechanisms that explain why chromatin replication is an important source of gene expression variability.
摘要:
DNA复制会导致染色质结构的整体混乱,需要数小时才能恢复。然而,这些染色质重排如何影响基因表达的调节和细胞身份的维持尚不清楚。这里,我们使用ChOR-seq和ChrRNA-seq实验来分析人细胞中染色质复制后最初小时的RNA聚合酶II(RNAPII)活性和新生RNA合成.我们观察到新生染色质中的转录伸长被迅速重新激活,但RNAPII的丰度和分布被改变,在RNA合成中产生异质变化。此外,这第一波转录导致RNAPII阻塞在复制叉后面,导致交替剪接的变化。总之,我们的研究结果加深了我们对细胞分裂过程中转录程序如何调节的理解,并揭示了解释染色质复制为何是基因表达变异性的重要来源的分子机制.