Comparative analysis of linker histone H1, MeCP2, and HMGD1 on nucleosome stability and target site accessibility.
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.
Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA.
Caitlyn
C
Riedmann
Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA.
Yvonne N
YN
Fondufe-Mittendorf
D000818:Animals; D004247:DNA; D029721:Drosophila Proteins / Q000737:chemistry*; D004331:Drosophila melanogaster; D006609:High Mobility Group Proteins / Q000737:chemistry*; D006657:Histones / Q000737:chemistry*; D051783:Methyl-CpG-Binding Protein 2 / Q000737:chemistry*; D008956:Models, Chemical; D009707:Nucleosomes / Q000737:chemistry*; D020218:Response Elements; D014157:Transcription Factors / Q000737:chemistry
D029721:Drosophila Proteins; C557617:GAL4 protein, Drosophila; D006609:High Mobility Group Proteins; D006657:Histones; C106685:HmgD protein, Drosophila; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D009707:Nucleosomes; D014157:Transcription Factors; D004247:DNA