title: Tagging methyl-CpG-binding domain proteins reveals different spatiotemporal expression and supports distinct functions.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  We analyzed behavioral phenotypes, generated biotin-tagged MBD1 and MBD2 knockin mice, and performed biochemical studies of MBD2-NuRD.
  
  
  RESULTS
  Most behavioral measures are minimally affected in Mbd2 knockout mice. In contrast to other MBDs, MBD2 shows distinct expression patterns.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Kathleen H
authors.initials: KH
authors.lastname: Wood
authors.affiliation: Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Johnson
authors.affiliation: Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Welsh
authors.affiliation: Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jun Y
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Krizman
authors.affiliation: Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Brodkin
authors.affiliation: Department of Pharmacology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Blendy
authors.affiliation: Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA.|Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Robinson
authors.affiliation: Department of Cell & Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Marisa S
authors.initials: MS
authors.lastname: Bartolomei
authors.affiliation: Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Zhaolan
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001679:Biogenic Amines / Q000032:analysis; D001835:Body Weight; D001921:Brain / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D055879:Gene Knock-In Techniques; D008297:Male; D018782:Maze Learning; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D062211:Spatio-Temporal Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001679:Biogenic Amines; D004268:DNA-Binding Proteins; C489323:Mbd1 protein, mouse; C489326:Mbd2 protein, mouse; C492013:Mbd3 protein, mouse; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D014157:Transcription Factors; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex
keywords: DNA methylation; DNA-binding protein; MBD1; MBD2; MeCP2; NuRD; chromatin regulation; gene knockout; methyl-CpG-binding domain protein; mouse genetics