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Functional compensation among HMGN variants modulates the DNase I hypersensitive sites at enhancers.
Genome Res. 25, 1295-1308 (2015)
DNase I hypersensitive sites (DHSs) are a hallmark of chromatin regions containing regulatory DNA such as enhancers and promoters; however, the factors affecting the establishment and maintenance of these sites are not fully understood. We now show that HMGN1 and HMGN2, nucleosome-binding proteins that are ubiquitously expressed in vertebrate cells, maintain the DHSs landscape of mouse embryonic fibroblasts (MEFs) synergistically. Loss of one of these HMGN variants led to a compensatory increase of binding of the remaining variant. Genome wide mapping of the DHSs in Hmgn1-/-, Hmgn2-/- and Hmgn1-/-n2-/- MEFs reveals that loss of both, but not a single HMGN variant, leads to significant remodeling of the DHSs landscape, especially at enhancer regions marked by H3K4me1 and H3K27ac. Loss of HMGN variants affects the induced expression of stress responsive genes in MEFs, the transcription profiles of several mouse tissues, and leads to altered phenotypes that are not seen in mice lacking only one variant. We conclude that the compensatory binding of HMGN variants to chromatin maintains the DHSs landscape and the transcription fidelity and is necessary to retain wild type phenotypes. Our study provides insights into mechanisms that maintain regulatory sites in chromatin and into functional compensation among nucleosome binding architectural proteins.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Chromosomal-protein Hmgn1; Histone H1; Chromatin Compaction; Linker Histone; Living Cells; Human Genome; Mobility; Binding; Nucleosomes; Transcription
ISSN (print) / ISBN 1088-9051
e-ISSN 1549-5469
Zeitschrift Genome Research
Quellenangaben Band: 25, Heft: 9, Seiten: 1295-1308 Artikelnummer: , Supplement: ,
Verlag Cold Spring Harbor Laboratory Press, HighWire Press
Verlagsort Cold Spring Harbor
Begutachtungsstatus peer-reviewed
Institut(e) Institute of Experimental Genetics (IEG)
Institute of Developmental Genetics (IDG)
German Center for Diabetes Reseach (DZD)