State Key Laboratory of Oncogenes and Related Genes, and Chinese Academy of Medical Sciences Research Unit (NO.2019RU043), Shanghai Cancer Institute, Renji hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200127, China.
Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai, 200025, China.
Cell Death Differ. 2022 Aug;29(8):1569-1581. doi: 10.1038/s41418-022-00944-x. Epub 2022 Feb 9.
Linker histone H1 proteins contain many variants in mammalian and can stabilize the condensed state of chromatin by binding to nucleosomes and promoting a more inaccessible structure of DNA. However, it is poorly understood how the binding of histone H1s to chromatin DNA is regulated. Screened as one of a collection of epithelial cells-enriched long non-coding RNAs (lncRNAs), here we found that small nucleolar RNA host gene 8 (SNHG8) is a chromatin-localized lncRNA and presents strong interaction and phase separation with histone H1 variants. Moreover, SNHG8 presents stronger ability to bind H1s than linker DNA, and outcompetes linker DNA for H1 binding. Consequently, loss of SNHG8 increases the amount of H1s that bind to chromatin, promotes chromatin condensation, and induces an epithelial differentiation-associated gene expression pattern. Collectively, our results propose that the highly abundant SNHG8 in epithelial cells keeps histone H1 variants out of nucleosome and its loss contributes to epithelial cell differentiation.
连接组蛋白 H1 蛋白在哺乳动物中有许多变体，通过与核小体结合并促进 DNA 更不易接近的结构，来稳定染色质的浓缩状态。然而，组蛋白 H1 与染色质 DNA 的结合是如何被调控的，目前还知之甚少。在这里，我们发现小核仁 RNA 宿主基因 8（SNHG8）是一种定位于染色质的长非编码 RNA，它作为上皮细胞中富集的长非编码 RNA（lncRNA）之一被筛选出来，与组蛋白 H1 变体有强烈的相互作用和相分离。此外，SNHG8 与 H1 变体的结合能力比连接 DNA 更强，并且与 H1 结合竞争连接 DNA。因此，SNHG8 的缺失增加了与染色质结合的 H1 数量，促进了染色质的浓缩，并诱导了上皮分化相关的基因表达模式。总的来说，我们的研究结果表明，上皮细胞中高丰度的 SNHG8 可使组蛋白 H1 变体远离核小体，而 SNHG8 的缺失有助于上皮细胞的分化。
