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High Mobility Group Nucleosome binding protein1 (HMGN1) is a dynamic player in differentiation and gene regulation
Author(s) -
Rand Eyal,
Cherukuri Srujana,
Bustin Michael
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.196
Subject(s) - chromatin , cellular differentiation , biology , microbiology and biotechnology , high mobility group , gene expression , histone , gene , genetics
Cellular differentiation involves specific changes in genome organization and chromatin structure. High Mobility Group Nucleosome binding proteins are architectural proteins that alter chromatin structure, compaction, and histone modifications. Previously we demonstrated that HMGN1 affects cellular differentiation and its expression is down‐regulated during development. To investigate the mechanism by which HMGN1 affects cellular differentiation, we followed the differentiation of embryonic stem (ES) cells into Neuronal Dopaminergic and Pancreatic Islet like pathways. In addition we generated Hmgn1 −/− ES and wild type ES stably over‐expressing elevated levels of HMGN1. Differentiation of the ES cells showed that HMGN1 mRNA and protein levels were markedly reduced in both differentiation pathways. We further tested whether knock‐down or over‐expression of HMGN1 alters the ability of these ES cell lines to undergo differentiation. While Hmgn1 −/− ES cells showed normal differentiation, ES cells over‐expressing HMGN1 were unable to differentiate along these pathways. This suggests that down‐regulation of HMGN1 is required for normal cellular differentiation. Based on these findings, we propose that HMGN proteins, through their chromatin modifying activity affect the cellular transcription profile and play a role in determining the differentiation potential of ES cells.