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BMC Genomics

, 15:92

Multicellular invertebrate genomics


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.

KeywordsChromatin structure Transcriptional regulation Histone H1 High mobility group protein Nucleosome repeat length AbbreviationsTSSTranscription start sites

PTMsPost translational modifications

ChIPChromatin immunoprecipitation

nuc-ChIP-seqNucleosome immunoprecipitation followed by next generation sequencing

MNaseMicrococcal nuclease

RT-PCRReal-time polymerase chain reaction.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-15-92 contains supplementary material, which is available to authorized users.

Narasimharao Nalabothula, Graham McVicker contributed equally to this work.

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Autor: Narasimharao Nalabothula - Graham McVicker - John Maiorano - Rebecca Martin - Jonathan K Pritchard - Yvonne N Fondufe-Mitt


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