Methyl-CpG-binding domain proteins: readers of the epigenome.
How DNA methylation is interpreted and influences genome regulation remains largely unknown. Proteins of the methyl-CpG-binding domain (MBD) family are primary candidates for the readout of DNA methylation as they recruit chromatin remodelers, histone deacetylases and methylases to methylated DNA associated with gene repression. MBD protein binding requires both functional MBD domains and methyl-CpGs; however, some MBD proteins also bind unmethylated DNA and active regulatory regions via alternative regulatory domains or interaction with the nucleosome remodeling deacetylase (NuRD/Mi-2) complex members. Mutations within MBD domains occur in many diseases, including neurological disorders and cancers, leading to loss of MBD binding specificity to methylated sites and gene deregulation. Here, we summarize the current state of knowledge about MBD proteins and their role as readers of the epigenome.
Epigenetics Research Laboratory, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
Qian
Q
Du
Epigenetics Research Laboratory, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
Phuc-Loi
PL
Luu
Epigenetics Research Laboratory, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.|St Vincent's Clinical School, University of NSW, Darlinghurst, NSW 2010, Australia.
Clare
C
Stirzaker
Epigenetics Research Laboratory, Genomics & Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.|St Vincent's Clinical School, University of NSW, Darlinghurst, NSW 2010, Australia.
Susan J
SJ
Clark
D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D020868:Gene Silencing; D020022:Genetic Predisposition to Disease; D006801:Humans; D005810:Multigene Family; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs
D004268:DNA-Binding Proteins
DNA methylation; MBD1; MBD2; MBD3; MBD4; MeCP2; cancer; epigenetics; methyl binding domain proteins