Title: Tagging methyl-CpG-binding domain proteins reveals different spatiotemporal expression and supports distinct functions.
Authors: Wood, Kathleen H; Johnson, Brian S; Welsh, Sarah A; Lee, Jun Y; Cui, Yue; Krizman, Elizabeth; Brodkin, Edward S; Blendy, Julie A; Robinson, Michael B; Bartolomei, Marisa S; Zhou, Zhaolan
Published In Epigenomics, (2016 Apr)
Abstract: DNA methylation is recognized by methyl-CpG-binding domain (MBD) proteins. Multiple MBDs are linked to neurodevelopmental disorders in humans and mice. However, the functions of MBD2 are poorly understood. We characterized Mbd2 knockout mice and determined spatiotemporal expression of MBDs and MBD2-NuRD (nucleosome remodeling deacetylase) interactions.We analyzed behavioral phenotypes, generated biotin-tagged MBD1 and MBD2 knockin mice, and performed biochemical studies of MBD2-NuRD.Most behavioral measures are minimally affected in Mbd2 knockout mice. In contrast to other MBDs, MBD2 shows distinct expression patterns.Unlike most MBDs, MBD2 is ubiquitously expressed in all tissues examined and appears dispensable for brain functions measured in this study. We provide novel genetic tools and reveal new directions to investigate MBD2 functions in vivo.
PubMed ID: 27066839
MeSH Terms: Animals; Behavior, Animal*; Biogenic Amines/analysis; Body Weight; Brain/metabolism; CpG Islands; DNA Methylation*; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism*; Female; Gene Expression Regulation; Gene Knock-In Techniques; Male; Maze Learning; Methyl-CpG-Binding Protein 2/genetics; Methyl-CpG-Binding Protein 2/metabolism*; Mi-2 Nucleosome Remodeling and Deacetylase Complex/genetics; Mi-2 Nucleosome Remodeling and Deacetylase Complex/metabolism*; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Spatio-Temporal Analysis; Transcription Factors/genetics; Transcription Factors/metabolism