The methyl-CpG-binding protein MeCP2 and neurological disease

2008 ◽  
Vol 36 (4) ◽  
pp. 575-583 ◽  
Author(s):  
Adrian Bird
Keyword(s):  
Dna Methylation ◽  
Rett Syndrome ◽  
Dna Sequences ◽  
Neurological Disease ◽  
Binding Protein ◽  
Autism Spectrum ◽  
Model Systems ◽  
Mecp2 Gene ◽  
Methylated Dna ◽  
Protein Mecp2

The methyl-CpG-binding protein MeCP2 was discovered over 15 years ago as part of a search for proteins that selectively bind methylated DNA. It is a nuclear protein that is largely chromatin-bound and has a strong preference for binding to methylated DNA sequences in vivo. Evidence from model systems shows that MeCP2 can recruit the Sin3a co-repressor complex to promoters leading to transcriptional repression, therefore suggesting that MeCP2 can interpret the DNA methylation signal to bring about gene silencing. Mutations in the human MECP2 gene cause the autism spectrum disorder Rett Syndrome. MeCP2 is most highly expressed in neurons, and mice lacking this protein show symptoms that strikingly parallel those of Rett patients. Surprisingly, these symptoms are efficiently reversed by delayed activation of a ‘stopped’ Mecp2 gene, raising hopes that human Rett syndrome may also be reversible. Future studies of MeCP2 promise to shed light upon brain function, neurological disease and the biology of DNA methylation.

scholarly journals The major histocompatibility complex class II promoter-binding protein RFX (NF-X) is a methylated DNA-binding protein.

1993 ◽  
Vol 13 (11) ◽  
pp. 6810-6818 ◽  
Author(s):  
X Y Zhang ◽  
N Jabrane-Ferrat ◽  
C K Asiedu ◽  
S Samac ◽  
B M Peterlin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Binding ◽  
Dna Sequences ◽  
Protein Complexes ◽  
Binding Protein ◽  
Dna Binding Protein ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Methylated Dna ◽  
Mammalian Protein

A mammalian protein called RFX or NF-X binds to the X box (or X1 box) in the promoters of a number of major histocompatibility (MHC) class II genes. In this study, RFX was shown to have the same DNA-binding specificity as methylated DNA-binding protein (MDBP), and its own cDNA was found to contain a binding site for MDBP in the leader region. MDBP is a ubiquitous mammalian protein that binds to certain DNA sequences preferentially when they are CpG methylated and to other related sequences, like the X box, irrespective of DNA methylation. MDBP from HeLa and Raji cells formed DNA-protein complexes with X-box oligonucleotides that coelectrophoresed with those containing standard MDBP sites. Furthermore, MDBP and X-box oligonucleotides cross-competed for the formation of these DNA-protein complexes. DNA-protein complexes obtained with MDBP sites displayed the same partial supershifting with an antiserum directed to the N terminus of RFX seen for complexes containing an X-box oligonucleotide. Also, the in vitro-transcribed-translated product of a recombinant RFX cDNA bound specifically to MDBP ligands and displayed the DNA methylation-dependent binding of MDBP. RFX therefore contains MDBP activity and thereby also EF-C, EP, and MIF activities that are indistinguishable from MDBP and that bind to methylation-independent sites in the transcriptional enhancers of polyomavirus and hepatitis B virus and to an intron of c-myc.

The major histocompatibility complex class II promoter-binding protein RFX (NF-X) is a methylated DNA-binding protein

1993 ◽  
Vol 13 (11) ◽  
pp. 6810-6818
Author(s):  
X Y Zhang ◽  
N Jabrane-Ferrat ◽  
C K Asiedu ◽  
S Samac ◽  
B M Peterlin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Binding ◽  
Dna Sequences ◽  
Protein Complexes ◽  
Binding Protein ◽  
Dna Binding Protein ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Methylated Dna ◽  
Mammalian Protein

A mammalian protein called RFX or NF-X binds to the X box (or X1 box) in the promoters of a number of major histocompatibility (MHC) class II genes. In this study, RFX was shown to have the same DNA-binding specificity as methylated DNA-binding protein (MDBP), and its own cDNA was found to contain a binding site for MDBP in the leader region. MDBP is a ubiquitous mammalian protein that binds to certain DNA sequences preferentially when they are CpG methylated and to other related sequences, like the X box, irrespective of DNA methylation. MDBP from HeLa and Raji cells formed DNA-protein complexes with X-box oligonucleotides that coelectrophoresed with those containing standard MDBP sites. Furthermore, MDBP and X-box oligonucleotides cross-competed for the formation of these DNA-protein complexes. DNA-protein complexes obtained with MDBP sites displayed the same partial supershifting with an antiserum directed to the N terminus of RFX seen for complexes containing an X-box oligonucleotide. Also, the in vitro-transcribed-translated product of a recombinant RFX cDNA bound specifically to MDBP ligands and displayed the DNA methylation-dependent binding of MDBP. RFX therefore contains MDBP activity and thereby also EF-C, EP, and MIF activities that are indistinguishable from MDBP and that bind to methylation-independent sites in the transcriptional enhancers of polyomavirus and hepatitis B virus and to an intron of c-myc.

scholarly journals Role of DNA Methyl-CpG-Binding Protein MeCP2 in Rett Syndrome Pathobiology and Mechanism of Disease

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 75
Author(s):  
Shervin Pejhan ◽  
Mojgan Rastegar
Keyword(s):  
Rett Syndrome ◽  
Binding Protein ◽  
Autism Spectrum ◽  
Cellular Systems ◽  
De Novo Mutation ◽  
Genetic Mutations ◽  
Mecp2 Gene ◽  
Altered Expression ◽  
The Brain

Rett Syndrome (RTT) is a severe, rare, and progressive developmental disorder with patients displaying neurological regression and autism spectrum features. The affected individuals are primarily young females, and more than 95% of patients carry de novo mutation(s) in the Methyl-CpG-Binding Protein 2 (MECP2) gene. While the majority of RTT patients have MECP2 mutations (classical RTT), a small fraction of the patients (atypical RTT) may carry genetic mutations in other genes such as the cyclin-dependent kinase-like 5 (CDKL5) and FOXG1. Due to the neurological basis of RTT symptoms, MeCP2 function was originally studied in nerve cells (neurons). However, later research highlighted its importance in other cell types of the brain including glia. In this regard, scientists benefitted from modeling the disease using many different cellular systems and transgenic mice with loss- or gain-of-function mutations. Additionally, limited research in human postmortem brain tissues provided invaluable findings in RTT pathobiology and disease mechanism. MeCP2 expression in the brain is tightly regulated, and its altered expression leads to abnormal brain function, implicating MeCP2 in some cases of autism spectrum disorders. In certain disease conditions, MeCP2 homeostasis control is impaired, the regulation of which in rodents involves a regulatory microRNA (miR132) and brain-derived neurotrophic factor (BDNF). Here, we will provide an overview of recent advances in understanding the underlying mechanism of disease in RTT and the associated genetic mutations in the MECP2 gene along with the pathobiology of the disease, the role of the two most studied protein variants (MeCP2E1 and MeCP2E2 isoforms), and the regulatory mechanisms that control MeCP2 homeostasis network in the brain, including BDNF and miR132.

scholarly journals The Methyl-CpG-binding Protein MeCP2 Links DNA Methylation to Histone Methylation

2002 ◽  
Vol 278 (6) ◽  
pp. 4035-4040 ◽  
Author(s):  
François Fuks ◽  
Paul J. Hurd ◽  
Daniel Wolf ◽  
Xinsheng Nan ◽  
Adrian P. Bird ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone Methylation ◽  
Binding Protein ◽  
Protein Mecp2

scholarly journals Effect of site-specific DNA methylation and mutagenesis on recognition by methylated DNA-binding protein from human placenta

1986 ◽  
Vol 14 (21) ◽  
pp. 8387-8397 ◽  
Author(s):  
Xian-Yang Zhang ◽  
Kenneth C. Ehrlich ◽  
Richard Y.-H. Wang ◽  
Melanie Ehrlich
Keyword(s):  
Dna Methylation ◽  
Dna Binding ◽  
Human Placenta ◽  
Binding Protein ◽  
Dna Binding Protein ◽  
Site Specific ◽  
Methylated Dna

The X-linked methylated DNA binding protein, Mecp2, is subject to X inactivation in the mouse

1995 ◽  
Vol 6 (8) ◽  
pp. 491-492 ◽  
Author(s):  
D. A. Adler ◽  
N. A. Quaderi ◽  
S. D. M. Brown ◽  
V. M. Chapman ◽  
J. Moore ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Protein ◽  
Dna Binding Protein ◽  
X Inactivation ◽  
Methylated Dna ◽  
Protein Mecp2
Sign in / Sign up

Export Citation Format

Share Document