title: CpG dinucleotide positioning patterns determine the binding affinity of methyl-binding domain to nucleosomes.
abstract: The methyl-binding domain of MBD1 is a common methyl CpG binding motif and has been linked to transcriptional repression. Understanding the dynamics of MBD1 binding to nucleosomal DNA is crucial, but the molecular interactions between MBD1 and chromatin remain elusive. In this study, we found the binding of MBD1 to nucleosomes demonstrates sequence preferences depending on the position of the methyl groups on the nucleosome. Specifically, binding was favored atmeCpG sites in the dyad proximal region and facing towards the histone octamers. At locations where themeCpG sites face away from the histone octamer, the binding affinity was significantly lower. Interestingly, the binding of ΔMBD1 at methylated CpG sites facing away from histone octamers induces conformational changes of nucleosomes, resulting in a more "open" conformation. The biological implication of DNA methylation is thus likely to be synergistically regulated via DNA sequences contents and their nucleosome-positioning patterns based on our in vitro findings.
authors.affiliation: Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47906, USA.
authors.forename: Agnes
authors.initials: A
authors.lastname: Mendonca
authors.affiliation: Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47906, USA.
authors.forename: Oscar F
authors.initials: OF
authors.lastname: Sanchez
authors.affiliation: Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47906, USA.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN 47906, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.affiliation: Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47906, USA; Purdue University Center for Cancer Research, West Lafayette, IN 47906, USA. Electronic address: cyuan@purdue.edu.
authors.forename: Chongli
authors.initials: C
authors.lastname: Yuan
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009707:Nucleosomes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000072417:Protein Domains; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; C066141:MBD1 protein, human; D009707:Nucleosomes; D014157:Transcription Factors
keywords: DNA methylation; Förster resonance energy transfer; MBD1; Nucleosome and chromatin