The chromatin binding protein HMGN1 regulates the expression of MeCP2 and affects the behavior of mice

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NCI	NEURO/BEHAV/SENSYS-1

* FARE Award Winner

Authors

• L Abuhatzira
• A Shamir
• DE Schones
• AA Schäffer
• M Busitn

Abstract

High Mobility Group N1 protein (HMGN1), a nucleosomal binding protein that affects the structure and function of chromatin, is encoded by a gene located on chromosome 21, and is overexpressed in Down syndrome patients. Misexpression of HMGN1 affects the cellular transcription profile, however, its possible role in Down syndrome is not known. Here we show that HMGN1 modulates the chromatin structure and expression of Methyl CpG binding Protein 2 (MeCP2), a DNA binding protein associated with the etiology of several neuro-developmental disorders including Autism. We demonstrate that altered expression of HMGN1 leads to changes in MeCP2 levels in brain tissue from mice that either over-express or lack HMGN1, indicating that HMGN1 is a negative regulator of MeCP2. Behavior analyses of these mice show abnormalities in activity, anxiety and social behavior. Targeted analysis of the Autism Genetic Resource Exchange genotype collection reveals abnormalities within 500 kbp of HMGN1, in a region affecting its expression. Our results link HMGN1 to some of the neurological phenotypes found in Down syndrome, and also suggest that misexpression of HMGN1 may contribute to the etiology of neuro-developmental disorders such as Autism.

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