The chromatin-binding protein HMGN3 stimulates histone acetylation and transcription across the Glyt1 gene

Barkess, G., Postnikov, Y., Campos, C.D., Mishra, S., Mohan, G., Verma, S., Bustin, M. and West, K.L. (2012) The chromatin-binding protein HMGN3 stimulates histone acetylation and transcription across the Glyt1 gene. Biochemical Journal, 442(3), pp. 495-505. (doi: 10.1042/BJ20111502) (PMID:22150271) (PMCID:PMC3713072)

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Abstract

HMGNs are nucleosome-binding proteins that alter the pattern of histone modifications and modulate the binding of linker histones to chromatin. The HMGN3 family member exists as two splice forms, HMGN3a which is full-length and HMGN3b which lacks the C-terminal RD (regulatory domain). In the present study, we have used the <i>Glyt1</i> (glycine transporter 1) gene as a model system to investigate where HMGN proteins are bound across the locus <i>in vivo</i>, and to study how the two HMGN3 splice variants affect histone modifications and gene expression. We demonstrate that HMGN1, HMGN2, HMGN3a and HMGN3b are bound across the <i>Glyt1</i> gene locus and surrounding regions, and are not enriched more highly at the promoter or putative enhancer. We conclude that the peaks of H3K4me3 (trimethylated Lys<sup>4</sup> of histone H3) and H3K9ac (acetylated Lys<sup>9</sup> of histone H3) at the active <i>Glyt1a</i> promoter do not play a major role in recruiting HMGN proteins. HMGN3a/b binding leads to increased H3K14 (Lys<sup>14</sup> of histone H3) acetylation and stimulates <i>Glyt1a</i> expression, but does not alter the levels of H3K4me3 or H3K9ac enrichment. Acetylation assays show that HMGN3a stimulates the ability of PCAF [p300/CREB (cAMP-response-element-binding protein)-binding protein-associated factor] to acetylate nucleosomal H3 <i>in vitro</i>, whereas HMGN3b does not. We propose a model where HMGN3a/b-stimulated H3K14 acetylation across the bodies of large genes such as <i>Glyt1</i> can lead to more efficient transcription elongation and increased mRNA production.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:West, Dr Katherine and Campos, Mrs Chrisanne and Barkess, Dr Grainne
Authors: Barkess, G., Postnikov, Y., Campos, C.D., Mishra, S., Mohan, G., Verma, S., Bustin, M., and West, K.L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Biochemical Journal
ISSN:0264-6021
ISSN (Online):1470-8728

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
392021Understanding how the chromatin protein HMGN3 regulates target gene expressionKatherine WestBiotechnology and Biological Sciences Research Council (BBSRC)BB/C006496/1RI CANCER SCIENCES