The chromatin architectural proteins HMGD1 and H1 bind reciprocally and have opposite effects on chromatin structure and gene regulation

BMC Genomics

Research Article

Graham McVicker¹  Jonathan K Pritchard²  Rebecca Martin³  Narasimharao Nalabothula⁴  John Maiorano⁴  Yvonne N Fondufe-Mittendorf⁴ 

[1] Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, 02115, Boston, MA, USA;Department of Genetics, Stanford University, 94305, Stanford, CA, USA;Department of Genetics, Stanford University, 94305, Stanford, CA, USA;Department of Biology, Stanford University, 94305, Stanford, CA, USA;Howard Hughes Medical Institute, Stanford University, 94305, Stanford, CA, USA;Department of Molecular Biosciences, Northwestern University, 60208, Evanston, IL, USA;Department of Molecular and Cellular Biochemistry, University of Kentucky, 40536, Lexington, KY, USA;

关键词: Chromatin structure;    Transcriptional regulation;    Histone H1;    High mobility group protein;    Nucleosome repeat length;   

DOI  :  10.1186/1471-2164-15-92

 received in 2014-01-29, accepted in 2014-01-30,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundChromatin architectural proteins interact with nucleosomes to modulate chromatin accessibility and higher-order chromatin structure. While these proteins are almost certainly important for gene regulation they have been studied far less than the core histone proteins.ResultsHere we describe the genomic distributions and functional roles of two chromatin architectural proteins: histone H1 and the high mobility group protein HMGD1 in Drosophila S2 cells. Using ChIP-seq, biochemical and gene specific approaches, we find that HMGD1 binds to highly accessible regulatory chromatin and active promoters. In contrast, H1 is primarily associated with heterochromatic regions marked with repressive histone marks. We find that the ratio of HMGD1 to H1 binding is a better predictor of gene activity than either protein by itself, which suggests that reciprocal binding between these proteins is important for gene regulation. Using knockdown experiments, we show that HMGD1 and H1 affect the occupancy of the other protein, change nucleosome repeat length and modulate gene expression.ConclusionCollectively, our data suggest that dynamic and mutually exclusive binding of H1 and HMGD1 to nucleosomes and their linker sequences may control the fluid chromatin structure that is required for transcriptional regulation. This study provides a framework to further study the interplay between chromatin architectural proteins and epigenetics in gene regulation.

【 授权许可】

Unknown   
© Nalabothula et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.