Abstract
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.
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Data availability
The RNA- and ATAC-seq data from this publication have been deposited to the GEO database (https://www.ncbi.nlm.nih.gov/geo) and assigned the identifiers GSE151626.
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Acknowledgements
We are grateful to Prof. Robert G. Roeder for providing p601 plasmid [66]. We thank Prof. Yongzhong Liu for providing pLKO.1-puro and pLVX-puro plasmids. This work was supported by National Natural Science Foundation (82103233, 82022053, 81972583) and its innovative group support (No. 81721004), National Key R&D Program of China (2020YFA0803403), CAMS Innovation Fund for Medical Sciences (CIFMS) (2019-I2M-5-051), and Shanghai Science and Technology Commission (20JC1410100).
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PH and CZ performed most experiments. YJ performed bioinformatics analysis. M-KG, NZ, and SY conducted partial experiments. YY and J-XY provided constructive comments and discussion. S-MS and G-QC designed and supervised the entire project and prepared the manuscript.
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He, P., Zhang, C., Ji, Y. et al. Epithelial cells-enriched lncRNA SNHG8 regulates chromatin condensation by binding to Histone H1s. Cell Death Differ 29, 1569–1581 (2022). https://doi.org/10.1038/s41418-022-00944-x
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DOI: https://doi.org/10.1038/s41418-022-00944-x
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