Abstract
Chromatin architectural proteins (CAPs) bind the entry/exit DNA of nucleosomes and linker DNA to form higher order chromatin structures with distinct transcriptional outcomes. How CAPs mediate nucleosome dynamics is not well understood. We hypothesize that CAPs regulate DNA target site accessibility through alteration of the rate of spontaneous dissociation of DNA from nucleosomes. We investigated the effects of histone H1, high mobility group D1 (HMGD1), and methyl CpG binding protein 2 (MeCP2), on the biophysical properties of nucleosomes and chromatin. We show that MeCP2, like the repressive histone H1, traps the nucleosome in a more compact mononucleosome structure. Furthermore, histone H1 and MeCP2 hinder model transcription factor Gal4 from binding to its cognate DNA site within the nucleosomal DNA. These results demonstrate that MeCP2 behaves like a repressor even in the absence of methylation. Additionally, MeCP2 behaves similarly to histone H1 and HMGD1 in creating a higher-order chromatin structure, which is susceptible to chromatin remodeling by ISWI. Overall, we show that CAP binding results in unique changes to nucleosome structure and dynamics.
Document Type
Article
Publication Date
9-14-2016
Digital Object Identifier (DOI)
https://doi.org/10.1038/srep33186
Funding Information
The core is supported by grant NIH/NIGMS COBRE grant P30 GM110787. This research was supported by grants to CR (NIH/NINDS 1F31NS092418-01A1) and YNF-M (NIEHS 1R01ES024478, NSF 1517986, and IRSF 2923).
Repository Citation
Riedmann, Caitlyn and Fondufe-Mittendorf, Yvonne N., "Comparative Analysis of Linker Histone H1, MeCP2, and HMGD1 on Nucleosome Stability and Target Site Accessibility" (2016). Molecular and Cellular Biochemistry Faculty Publications. 98.
https://uknowledge.uky.edu/biochem_facpub/98
Supplementary Information: Supplemental Figure 1-6
Notes/Citation Information
Published in Scientific Reports, v. 6, article no. 33186, p. 1-11.
© The Author(s) 2016
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