序列特异性 RNA 结合蛋白诱导的聚合酶暂停驱动异染色质组装。

Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94158, USA.

Chan-Zuckerberg Biohub, San Francisco, California 94158, USA.

Genes Dev. 2018 Jul 1;32(13-14):953-964. doi: 10.1101/gad.310136.117.

In , transcripts derived from the pericentromeric and repeats promote heterochromatin formation via RNAi as well as an RNAi-independent mechanism involving the RNA polymerase II (RNAPII)-associated RNA-binding protein Seb1 and RNA processing activities. We show that Seb1 promotes long-lived RNAPII pauses at pericentromeric repeat regions and that their presence correlates with the heterochromatin-triggering activities of the corresponding and DNA fragments. Globally increasing RNAPII stalling by other means induces the formation of novel large ectopic heterochromatin domains. Such ectopic heterochromatin occurs even in cells lacking RNAi. These results uncover Seb1-mediated polymerase stalling as a signal necessary for heterochromatin nucleation.

在中，源自着丝粒的和重复序列通过 RNAi 以及涉及 RNA 聚合酶 II（RNAPII）相关 RNA 结合蛋白 Seb1 和 RNA 加工活性的非 RNAi 机制促进异染色质形成。我们表明，Seb1 促进长寿命的 RNA 聚合酶 II 在着丝粒重复区域的暂停，并且它们的存在与相应的和 DNA 片段的异染色质触发活性相关。通过其他手段全局增加 RNA 聚合酶 II 的暂停会诱导新的大型异位异染色质域的形成。即使在缺乏 RNAi 的细胞中也会发生这种异位异染色质。这些结果揭示了 Seb1 介导的聚合酶暂停作为异染色质成核所必需的信号。