美国国立卫生研究院Shiv I.S. Grewal课题组研究揭示了异染色质在核外周的定位抑制组蛋白的更新，从而促进表观遗传。2019年12月26日，《细胞》杂志发表了这项成果。

他们确定核边缘蛋白Amo1NUPL2是异质染色质在裂殖酵母基因组中的内源性和异位点传播所需的一个因子。Amo1与包含Rix1PELP1的RNA加工复合物RIXC和组蛋白伴侣复合物FACT相关。RIXC通过沉默的染色体结构域与异染色质蛋白Swi6HP1结合，并与周围的边界元件结合，在核外围将异染色质与Amo1连接起来。反过来，富含Amo1的亚结构域对于Swi6与FACT的关联至关重要，FACT阻止了组蛋白更新，以促进基因沉默并保持异染色质的表观遗传稳定性。

除了揭示异染色质核周定位所需的保守因素外，这些分析还阐明了一种机制，外围亚结构域通过该机制强制稳定基因抑制并以可遗传的方式维持异染色质。

据悉，在真核生物中，异染色质通常位于核外围。这项研究展示了核周定位对异染色质维持和基因沉默的生物学意义。

附：英文原文

Title: Positioning Heterochromatin at the Nuclear Periphery Suppresses Histone Turnover to Promote Epigenetic Inheritance

Author: Sahana Holla, Jothy Dhakshnamoorthy, H. Diego Folco, Vanivilasini Balachandran, Hua Xiao, Ling-ling Sun, David Wheeler, Martin Zofall, Shiv I.S. Grewal

Issue&Volume: December 26, 2019

Abstract: In eukaryotes, heterochromatin is generally located at the nuclear periphery. This study investigates the biological significance of perinuclear positioning for heterochromatin maintenance and gene silencing. We identify the nuclear rim protein Amo1 NUPL2 as a factor required for the propagation of heterochromatin at endogenous and ectopic sites in the fission yeast genome. Amo1 associates with the Rix1 PELP1-containing RNA processing complex RIXC and with the histone chaperone complex FACT. RIXC, which binds to heterochromatin protein Swi6 HP1 across silenced chromosomal domains and to surrounding boundary elements, connects heterochromatin with Amo1 at the nuclear periphery. In turn, the Amo1-enriched subdomain is critical for Swi6 association with FACT that precludes histone turnover to promote gene silencing and preserve epigenetic stability of heterochromatin. In addition to uncovering conserved factors required for perinuclear positioning of heterochromatin, these analyses elucidate a mechanism by which a peripheral subdomain enforces stable gene repression and maintains heterochromatin in a heritable manner.

DOI: 10.1016/j.cell.2019.12.004

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31330-3