Background: Chromatin 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. Results: Here 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. Conclusion: Collectively, 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.
|State||Published - Feb 1 2014|
Bibliographical noteFunding Information:
We thank Prof. Andrew Travers for the HMGD1 serum antibody used in initial western blot analyses. We also thank Prof. Authur Skoultchi for the H1 RNAi plasmid. We thank the staff of the Northwestern University Genomic Core and University of Chicago Genomic Facility for DNA sequencing. This research was supported by NIH grants U01 HG 007036 and the Howard Hughes Medical Institute JP and 2P20 RR020171 (YNF-M).
- Chromatin structure
- High mobility group protein
- Histone H1
- Nucleosome repeat length
- Transcriptional regulation
ASJC Scopus subject areas