The Human Proteins MBD5 and MBD6 Associate with Heterochromatin but They Do Not Bind Methylated DNA
Open Access
- 6 August 2010
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 5 (8), e11982
- https://doi.org/10.1371/journal.pone.0011982
Abstract
MBD5 and MBD6 are two uncharacterized mammalian proteins that contain a putative Methyl-Binding Domain (MBD). In the proteins MBD1, MBD2, MBD4, and MeCP2, this domain allows the specific recognition of DNA containing methylated cytosine; as a consequence, the proteins serve as interpreters of DNA methylation, an essential epigenetic mark. It is unknown whether MBD5 or MBD6 also bind methylated DNA; this question has interest for basic research, but also practical consequences for human health, as MBD5 deletions are the likely cause of certain cases of mental retardation. Here we report the first functional characterization of MBD5 and MBD6. We have observed that the proteins colocalize with heterochromatin in cultured cells, and that this localization requires the integrity of their MBD. However, heterochromatic localization is maintained in cells with severely decreased levels of DNA methylation. In vitro, neither MBD5 nor MBD6 binds any of the methylated sequences DNA that were tested. Our data suggest that MBD5 and MBD6 are unlikely to be methyl-binding proteins, yet they may contribute to the formation or function of heterochromatin. One isoform of MBD5 is highly expressed in oocytes, which suggests a possible role in epigenetic reprogramming after fertilization.Keywords
This publication has 45 references indexed in Scilit:
- Pathogenic Mechanisms of a Polyglutamine-mediated Neurodegenerative Disease, Spinocerebellar Ataxia Type 1Published by Elsevier BV ,2009
- Regulation of Set9-Mediated H4K20 Methylation by a PWWP Domain ProteinMolecular Cell, 2009
- The Methyl-CpG Binding Proteins Mecp2, Mbd2 and Kaiso Are Dispensable for Mouse Embryogenesis, but Play a Redundant Function in Neural DifferentiationPLOS ONE, 2009
- DNA methylation landscapes: provocative insights from epigenomicsNature Reviews Genetics, 2008
- Epilepsy and electroencephalographic anomalies in chromosome 2 aberrations: A reviewEpilepsy Research, 2008
- MeCP2 Binding to DNA Depends upon Hydration at Methyl-CpGMolecular Cell, 2008
- The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNANature, 2007
- Copy-Number Variations Measured by Single-Nucleotide–Polymorphism Oligonucleotide Arrays in Patients with Mental RetardationAmerican Journal of Human Genetics, 2007
- Stability and flexibility of epigenetic gene regulation in mammalian developmentNature, 2007
- A Family of Human Zinc Finger Proteins That Bind Methylated DNA and Repress TranscriptionMolecular and Cellular Biology, 2006