Biophysical characterization of the basic cluster in the transcription repression domain of human MeCP2 with AT-rich DNA

Biochem Biophys Res Commun. 2018 Jan 1;495(1):145-150. doi: 10.1016/j.bbrc.2017.10.169. Epub 2017 Oct 31.

Abstract

MeCP2 is a chromatin associated protein which is highly expressed in brain and relevant with Rett syndrome (RTT). There are AT-hook motifs in MeCP2 which can bind with AT-rich DNA, suggesting a role in chromatin binding. Here, we report the identification and characterization of another AT-rich DNA binding motif (residues 295 to 313) from the C-terminal transcription repression domain of MeCP2 by nuclear magnetic resonance (NMR) and isothermal calorimetry (ITC). This motif shows a micromolar affinity to AT-rich DNA, and it binds to the minor groove of DNA like AT-hook motifs. Together with the previous studies, our results provide an insight into a critical role of this motif in chromatin structure and function.

Keywords: AT-Hook; AT-rich DNA binding; Basic cluster; Methyl-CpG-binding protein 2; Transcription repression domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Binding Sites
  • DNA / chemistry
  • DNA / metabolism*
  • Humans
  • Methyl-CpG-Binding Protein 2 / chemistry*
  • Methyl-CpG-Binding Protein 2 / metabolism*
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Domains
  • Rett Syndrome / metabolism

Substances

  • Methyl-CpG-Binding Protein 2
  • DNA