Tagging methyl-CpG-binding domain proteins reveals different spatiotemporal expression and supports distinct functions

Epigenomics. 2016 Apr;8(4):455-73. doi: 10.2217/epi-2015-0004. Epub 2016 Apr 12.

Abstract

Aim: 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.

Experimental procedures: 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.

Conclusion: 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.

Keywords: DNA methylation; DNA-binding protein; MBD1; MBD2; MeCP2; NuRD; chromatin regulation; gene knockout; methyl-CpG-binding domain protein; mouse genetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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

Substances

  • Biogenic Amines
  • DNA-Binding Proteins
  • Mbd1 protein, mouse
  • Mbd2 protein, mouse
  • Mbd3 protein, mouse
  • Mecp2 protein, mouse
  • Methyl-CpG-Binding Protein 2
  • Transcription Factors
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex