Methyl CpG Binding Domain as a Protein Interaction Partner in Promoter Regulation and Neurodevelopment Through Evolutionary Expanded Entanglement.

Document Type

Article

Publication Date

2025

Publication Title

American journal of physiology. Cell physiology

Abstract

There is increasing evidence that the methyl-binding domain (MBD) is a protein-protein interaction motif that can function independently of methylated DNA binding. The MBD proteins found throughout plants and invertebrates duplicated into multiple vertebrate DNA and non-DNA binding members (MBD1, MBD2, MBD3, MBD4, MBD5, MBD6, MECP2, BAZ2A, BAZ2B, SETDB1, SETDB2). While many invertebrate species possess MBD proteins that can bind and recognize DNA methylation, the DNA-binding function has been independently lost multiple times, with only minor alterations to the protein interaction residues. The nucleosome remodeling and deacetylase (NuRD) complex, which interacts with MBD2/3 and is colocalized with MBD1/4 ChIP-Seq, is maintained in species where MBD2/3 cannot bind to DNA. NuRD ChIP-seq data from HepG2 cell line, human iPSCs, and human iPSC-derived liver cells suggest that the NuRD complex is highly localized to non-methylated CpG-rich housekeeping gene promoter elements, which are essential in organogenesis and maintained within the

DOI

10.1152/ajpcell.00749.2024

ISSN

1522-1563

PubMed ID

40712661

Link to Full Text

Share

COinS