Antithetic Effects of MBD2a on Gene Regulation

  • Fujita H
  • Fujii R
  • Aratani S
  • et al.
52Citations
Citations of this article
34Readers
Mendeley users who have this article in their library.

Abstract

DNA methylation is essential for epigenetic gene regulation during development. The cyclic AMP (cAMP)-responsive element (CRE) is found in the promoter of many cAMP-regulated genes and plays important roles in their gene expression. Methylation occurs on the CRE site and results in transcriptional repression via a direct mechanism, that is, prevention by the methyl group of binding of the cAMP-responsive factor CREB to this site. A recent study indicated that the nucleosome is also important in repressing transcription. In this study, we investigated the regulation of transcriptional repression on methylated CRE. We focused on methyl-CpG binding domain protein 2 (MBD2). MBD2 consists of two forms, MBD2a and MBD2b, the latter lacking the N-terminal extension of MBD2a. Unexpectedly, we found that MBD2a, but not MBD2b, promoted activation of the unmethylated cAMP-responsive genes. An in vivo binding assay revealed that MBD2a selectively interacted with RNA helicase A (RHA), a component of CREB transcriptional coactivator complexes. MBD2a and RHA cooperatively enhanced CREB-dependent gene expression. Interestingly, coimmunoprecipitation assays demonstrated that MBD2a binding to RHA was not associated with histone deacetylase 1. Our results indicate a novel role for MBD2a in gene regulation.

References Powered by Scopus

DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development

4933Citations
N/AReaders
Get full text

Targeted mutation of the DNA methyltransferase gene results in embryonic lethality

3399Citations
N/AReaders
Get full text

Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133

2247Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Methyl-CpG-binding domain proteins: Readers of the epigenome

354Citations
N/AReaders
Get full text

Epigenetic regulation of the neural transcriptome: The meaning of the marks

193Citations
N/AReaders
Get full text

Epigenetic tête-à-tête: The bilateral relationship between chromatin modifications and DNA methylation

124Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Fujita, H., Fujii, R., Aratani, S., Amano, T., Fukamizu, A., & Nakajima, T. (2003). Antithetic Effects of MBD2a on Gene Regulation. Molecular and Cellular Biology, 23(8), 2645–2657. https://doi.org/10.1128/mcb.23.8.2645-2657.2003

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 12

46%

Professor / Associate Prof. 9

35%

Researcher 4

15%

Lecturer / Post doc 1

4%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 12

48%

Biochemistry, Genetics and Molecular Bi... 9

36%

Neuroscience 2

8%

Medicine and Dentistry 2

8%

Article Metrics

Tooltip
Mentions
References: 2
Social Media
Shares, Likes & Comments: 131

Save time finding and organizing research with Mendeley

Sign up for free