Zofall Martin, Grewal Shiv I S
Laboratory of Molecular Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Mol Cell. 2006 Jun 9;22(5):681-92. doi: 10.1016/j.molcel.2006.05.010.
Heterochromatin formation is generally thought to result in transcriptional repression of target loci. However, RNAi-mediated heterochromatin assembly requires RNA polymerase II (Pol II) transcription. The mechanism facilitating Pol II accessibility to heterochromatin is unknown. We show that the fission yeast Epe1, a JmjC domain-containing protein and a negative regulator of heterochromatin, is distributed across all major heterochromatic domains and at certain meiotic genes. Remarkably, Epe1 is recruited to heterochromatic loci by the heterochromatin protein Swi6/HP1. Moreover, Epe1 acts in a heterochromatin-specific context to promote Pol II accessibility by counteracting repressive chromatin. This requires Epe1's JmjC domain, although the mechanism utilized might be distinct from other JmjC proteins that possess known demethylase activities. We also find that Epe1 is preferentially recruited to inverted repeats flanking centromeres to restrain the spread of pericentromeric heterochromatin. Our analyses suggest that Swi6/HP1 recruits opposing chromatin-modifying activities, the balancing of which is crucial for heterochromatin maintenance.
一般认为异染色质的形成会导致靶基因座的转录抑制。然而，RNA干扰介导的异染色质组装需要RNA聚合酶II（Pol II）转录。促进Pol II接近异染色质的机制尚不清楚。我们发现，裂殖酵母Epe1是一种含JmjC结构域的蛋白，也是异染色质的负调控因子，它分布在所有主要的异染色质结构域以及某些减数分裂基因处。值得注意的是，Epe1被异染色质蛋白Swi6/HP1招募到异染色质位点。此外，Epe1在异染色质特异性环境中发挥作用，通过对抗抑制性染色质来促进Pol II的可及性。这需要Epe1的JmjC结构域，尽管所利用的机制可能与其他具有已知去甲基酶活性的JmjC蛋白不同。我们还发现，Epe1优先被招募到着丝粒两侧的反向重复序列，以抑制着丝粒周围异染色质的扩散。我们的分析表明，Swi6/HP1招募了相反的染色质修饰活性，它们之间的平衡对于异染色质的维持至关重要。
