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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
Cèl·lules canceroses
Càncer de mama
Cancer cells
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.
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It is part of: Nucleic Acids Research, 2017, vol. 45, num. 20, p. 11622-11642
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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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