Characterization of MeCP2, a Vertebrate DNA Binding Protein with Affinity for Methylated DNA

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 1992 Oct 11

PMID 1408825

Citations 192

Authors

R R Meehan

J D Lewis

A P Bird

Affiliations

Soon will be listed here.

Abstract

Methylated DNA in vertebrates is associated with transcriptional repression and inactive chromatin. Two activities have been identified, MeCP1 and MeCP2, which bind specifically to DNA containing methyl-CpG pairs. In this report we characterize MeCP2. We show that it is more abundant than MeCP1, is more tightly bound in the nucleus, and is distinguishable chromatographically. The two proteins share widespread expression in somatic mammalian cells, and barely detectable expression in early embryonic cells. DNAs containing thymidine which has a methyl group at position 5 are not ligands for the MeCPs. The possible role of MeCP2 in methylation-associated gene inactivation was tested in in vitro transcription extracts. Purified MeCP2 inhibited transcription from both methylated and nonmethylated DNA templates in vitro, probably due to the presence of nonspecific DNA binding domains within the protein. We hypothesise that MeCP2 normally binds methylated DNA in the context of chromatin, contributing to the long-term repression and nuclease-resistance of methyl-CpGs.

Citing Articles

Diabetes-Driven Atherosclerosis: Updated Mechanistic Insights and Novel Therapeutic Strategies.

Karakasis P, Theofilis P, Patoulias D, Vlachakis P, Antoniadis A, Fragakis N Int J Mol Sci. 2025; 26(5).

PMID: 40076813 PMC: 11900163. DOI: 10.3390/ijms26052196.

Unveiling Molecular Dynamics of MeCp2, CDKL5 and BDNF in the Hippocampus of Individuals With Intractable Mesial Temporal Lobe Epilepsy.

Meshkinkhood N, Barati Dowom P, Noorbakhsh F, Ghadipasha M, Gharehdaghi J, Kellinghaus C J Cell Mol Med. 2025; 29(3):e70373.

PMID: 39888294 PMC: 11783159. DOI: 10.1111/jcmm.70373.

Integrated gene expression and alternative splicing analysis in human and mouse models of Rett syndrome.

Gioiosa S, Gasparini S, Presutti C, Rinaldi A, Castrignano T, Mannironi C Sci Rep. 2025; 15(1):2778.

PMID: 39843543 PMC: 11754816. DOI: 10.1038/s41598-025-86114-8.

Atherosclerosis in diabetes mellitus: novel mechanisms and mechanism-based therapeutic approaches.

Khan A, Jandeleit-Dahm K Nat Rev Cardiol. 2025; .

PMID: 39805949 DOI: 10.1038/s41569-024-01115-w.

Chromatin and transcription in Nucleic Acids Research: the first 50 years.

Defossez P Nucleic Acids Res. 2024; 52(22):13485-13489.

PMID: 39607690 PMC: 11662935. DOI: 10.1093/nar/gkae1151.

References

Pech M, Zachau H . Nucleotide sequence of a highly repetitive component of rat DNA. Nucleic Acids Res. 1979; 7(2):417-32. PMC: 328026. DOI: 10.1093/nar/7.2.417. View

Dignam J, Lebovitz R, Roeder R . Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983; 11(5):1475-89. PMC: 325809. DOI: 10.1093/nar/11.5.1475. View

Hsieh C, Lieber M . CpG methylated minichromosomes become inaccessible for V(D)J recombination after undergoing replication. EMBO J. 1992; 11(1):315-25. PMC: 556452. DOI: 10.1002/j.1460-2075.1992.tb05054.x. View

Lewis J, Meehan R, Henzel W, Jeppesen P, Klein F, Bird A . Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. Cell. 1992; 69(6):905-14. DOI: 10.1016/0092-8674(92)90610-o. View

Lewis J, Bird A . DNA methylation and chromatin structure. FEBS Lett. 1991; 285(2):155-9. DOI: 10.1016/0014-5793(91)80795-5. View

JANTSCH M, Hamilton B, Mayr B, Schweizer D . Meiotic chromosome behaviour reflects levels of sequence divergence in Sus scrofa domestica satellite DNA. Chromosoma. 1990; 99(5):330-5. DOI: 10.1007/BF01731720. View

Meehan R, Lewis J, McKay S, Kleiner E, Bird A . Identification of a mammalian protein that binds specifically to DNA containing methylated CpGs. Cell. 1989; 58(3):499-507. DOI: 10.1016/0092-8674(89)90430-3. View

Keshet I, Lieman-Hurwitz J, Cedar H . DNA methylation affects the formation of active chromatin. Cell. 1986; 44(4):535-43. DOI: 10.1016/0092-8674(86)90263-1. View

Busslinger M, Hurst J, Flavell R . DNA methylation and the regulation of globin gene expression. Cell. 1983; 34(1):197-206. DOI: 10.1016/0092-8674(83)90150-2. View

10.

Solage A, Cedar H . Organization of 5-methylcytosine in chromosomal DNA. Biochemistry. 1978; 17(14):2934-8. DOI: 10.1021/bi00607a036. View

11.

Bradford M . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72:248-54. DOI: 10.1016/0003-2697(76)90527-3. View

12.

Boyes J, Bird A . Repression of genes by DNA methylation depends on CpG density and promoter strength: evidence for involvement of a methyl-CpG binding protein. EMBO J. 1992; 11(1):327-33. PMC: 556453. DOI: 10.1002/j.1460-2075.1992.tb05055.x. View

13.

Bird A . The essentials of DNA methylation. Cell. 1992; 70(1):5-8. DOI: 10.1016/0092-8674(92)90526-i. View

14.

Levine A, CANTONI G, Razin A . Inhibition of promoter activity by methylation: possible involvement of protein mediators. Proc Natl Acad Sci U S A. 1991; 88(15):6515-8. PMC: 52116. DOI: 10.1073/pnas.88.15.6515. View

15.

Boyes J, Bird A . DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein. Cell. 1991; 64(6):1123-34. DOI: 10.1016/0092-8674(91)90267-3. View

16.

Pawlak A, Bryans M, Jost J . An avian 40 KDa nucleoprotein binds preferentially to a promoter sequence containing one single pair of methylated CpG. Nucleic Acids Res. 1991; 19(5):1029-34. PMC: 333776. DOI: 10.1093/nar/19.5.1029. View

17.

Antequera F, MacLeod D, Bird A . Specific protection of methylated CpGs in mammalian nuclei. Cell. 1989; 58(3):509-17. DOI: 10.1016/0092-8674(89)90431-5. View

18.

Wang R, Zhang X, Ehrlich M . A human DNA-binding protein is methylation-specific and sequence-specific. Nucleic Acids Res. 1986; 14(4):1599-614. PMC: 339531. DOI: 10.1093/nar/14.4.1599. View

19.

Cedar H . DNA methylation and gene activity. Cell. 1988; 53(1):3-4. DOI: 10.1016/0092-8674(88)90479-5. View

20.

Burton D, Butler M, Hyde J, Phillips D, Skidmore C, Walker I . The interaction of core histones with DNA: equilibrium binding studies. Nucleic Acids Res. 1978; 5(10):3643-63. PMC: 342701. DOI: 10.1093/nar/5.10.3643. View