Maintenance of active chromatin states by Hmgn1 and Hmgn2 is required for stem cell identity

Garza Manero, S. et al. (2019) Maintenance of active chromatin states by Hmgn1 and Hmgn2 is required for stem cell identity. Epigenetics and Chromatin, (Accepted for Publication)

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Abstract

Chromatin plasticity is thought to be fundamental to the pluripotency of embryonic stem cells. Hmgn proteins modulate chromatin structure and are highly expressed during early development and in neural stem/progenitor cells of the developing and adult brain. Here, we show that loss of Hmgn1 or Hmgn2 in pluripotent embryonal carcinoma cells leads to increased levels of spontaneous neuronal differentiation. This is accompanied by the loss of pluripotency markers and increased expression of the pro-neural transcription factors Neurog1 and Ascl1. Neural stem cells derived from these Hmgn-knockout lines also show increased spontaneous neuronal differentiation and Neurog1 expression. The loss of Hmgn2 is associated with the disruption of active chromatin states at specific classes of gene. The levels of H3K4me3, H3K9ac, H3K27ac and H3K122ac are considerably reduced at the pluripotency genes Nanog and Oct4, which impacts transcription. At endodermal/mesodermal lineage-specific genes, the loss of Hmgn2 leads to a switch from a bivalent to a repressive chromatin configuration. However, at the neuronal lineage genes Neurog1 and Ascl1, no epigenetic changes are observed and their bivalent states are retained. We conclude that Hmgn proteins play important roles in maintaining chromatin plasticity in stem cells, and are essential for maintaining stem cell identity and pluripotency.

Item Type:Articles (Other)
Status:Accepted for Publication
Refereed:No
Glasgow Author(s) Enlighten ID:West, Dr Adam and Garza Manero, Sylvia and West, Dr Katherine and Gurden, Ross and Jeantet, Valentine and SINDI, Abdulmajeed
Authors: Garza Manero, S., Sindi, A. A. A., Mohan, G., Rehbini, O., Jeantet, V. H.M., Bailo, M., Abdul Latif, F., West, M. P., Gurden, R., Finlayson, L., Svambaryte, S., West, A. G., and West, K. L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Life Sciences
Research Group:Katherine West
Journal Name:Epigenetics and Chromatin
Publisher:BioMed Central
ISSN:1756-8935
ISSN (Online):1756-8935
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
581981The role of H2B ubiquitination in genome organisation.Adam WestBiotechnology and Biological Sciences Research Council (BBSRC)BB/J008605/1ICS - EPIGENETICS
632343MRC Doctoral Training Grant 2013/14, 2014/15 and 2015/16George BaillieMedical Research Council (MRC)MR/K501335/1MVLS GRADUATE SCHOOL