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Title: | Histone H1 depletion triggers an interferon response in cancer cells via activation of heterochromatic repeats |
Author: | Izquierdo Bouldstridge, Andrea Bustillos Ortiz, Alcides Alberto Bonet-Costa, Carles Aribau-Miralbés, Patricia García-Gomis, Daniel Dabad, Marc Esteve Codina, Anna Pascual-Reguant, Laura Peiró, Sandra Esteller, Manel Murtha, Matthew Millán-Ariño, Lluís Jordan Vallès, Albert |
Keywords: | Interferó Histones Cèl·lules canceroses Heterocromatina Càncer de mama Interferon Histones Cancer cells Heterochromatin Breast cancer |
Issue Date: | 16-Nov-2017 |
Publisher: | Oxford University Press |
Abstract: | Histone H1 has seven variants in human somatic cells and contributes to chromatin compaction and transcriptional regulation. Knock-down (KD) of each H1 variant in breast cancer cells results in altered gene expression and proliferation differently in a variant specific manner with H1.2 and H1.4 KDs being most deleterious. Here we show combined depletion of H1.2 and H1.4 has a strong deleterious effect resulting in a strong interferon (IFN) response, as evidenced by an up-regulation of many IFN-stimulated genes (ISGs) not seen in individual nor in other combinations of H1 variant KDs. Although H1 participates to repress ISG promoters, IFN activation upon H1.2 and H1.4 KD is mainly generated through the activation of the IFN response by cytosolic nucleic acid receptors and IFN synthesis, and without changes in histone modifications at induced ISG promoters. H1.2 and H1.4 co-KD also promotes the appearance of accessibility sites genome wide and, particularly, at satellites and other repeats. The IFN response may be triggered by the expression of noncoding RNA generated from heterochromatic repeats or endogenous retroviruses upon H1 KD. In conclusion, redundant H1-mediated silencing of heterochromatin is important to maintain cell homeostasis and to avoid an unspecific IFN response. |
Note: | Reproducció del document publicat a: https://doi.org/10.1093/nar/gkx746 |
It is part of: | Nucleic Acids Research, 2017, vol. 45, num. 20, p. 11622-11642 |
URI: | http://hdl.handle.net/2445/122088 |
Related resource: | https://doi.org/10.1093/nar/gkx746 |
ISSN: | 0305-1048 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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