Methylated DNA Sequences in Genomic Imprinting

2000 ◽  
Vol 10 (3-4) ◽  
Author(s):  
Jeffrey R. Mann ◽  
Piroska E. Szabo ◽  
Michael R. Reed ◽  
Judith Singer-Sam
Keyword(s):  
Genomic Imprinting ◽  
Dna Sequences ◽  
Methylated Dna

Methylated DNA Sequences in Genomic Imprinting

2000 ◽  
Vol 10 (3-4) ◽  
pp. 18 ◽  
Author(s):  
Jeffrey R. Mann ◽  
Piroska E. Szabo ◽  
Michael R. Reed ◽  
Judith Singer-Sam
Keyword(s):  
Genomic Imprinting ◽  
Dna Sequences ◽  
Methylated Dna

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.

scholarly journals Towards Clinical Application of Methylated DNA Sequences as Cancer Biomarkers: A Joint NCI's EDRN and NIST Workshop on Standards, Methods, Assays, Reagents and Tools

2007 ◽  
Vol 67 (10) ◽  
pp. 4545-4549 ◽  
Author(s):  
Jacob Kagan ◽  
Sudhir Srivastava ◽  
Peter E. Barker ◽  
Steven A. Belinsky ◽  
Paul Cairns
Keyword(s):  
Clinical Application ◽  
Dna Sequences ◽  
Cancer Biomarkers ◽  
Methylated Dna

scholarly journals Influence of CpG methylation and target spacing on V(D)J recombination in a transgenic substrate

1993 ◽  
Vol 13 (1) ◽  
pp. 571-577
Author(s):  
P Engler ◽  
A Weng ◽  
U Storb
Keyword(s):  
Bone Marrow ◽  
Transgenic Mice ◽  
Lymph Nodes ◽  
Brain Tissue ◽  
Dna Sequences ◽  
Modifier Gene ◽  
One Dimensional ◽  
Methylated Dna ◽  
Recombination Signal Sequences ◽  
Target Spacing

We have previously described a line of transgenic mice with multiple head-to-tail copies of an artificial V-J recombination substrate and have shown that the methylation of this transgene is under the control of a dominant strain-specific modifier gene, Ssm-1. When the transgene array is highly methylated, no recombination is detectable, but when it is unmethylated, V-J joining is seen in the spleen, bone marrow, lymph nodes, and Peyer's patches but not in the thymus or nonlymphoid tissues, including brain tissue. Strikingly, in mice with partially methylated transgene arrays, rearrangement preferentially occurs in hypomethylated copies. Therefore, V-J recombination is negatively correlated with methylated DNA sequences. In addition, it appears that recombination occurs randomly between any two recombination signal sequences within the transgene array. This lack of target preference in an unselectable array of identical targets rules out simple mechanisms of one-dimensional tracking of a V(D)J recombinase complex.

scholarly journals Genomic Imprinting Controls Matrix Attachment Regionsin the Igf2Gene

2003 ◽  
Vol 23 (24) ◽  
pp. 8953-8959 ◽  
Author(s):  
Michaël Weber ◽  
Hélène Hagège ◽  
Adele Murrell ◽  
Claude Brunel ◽  
Wolf Reik ◽  
...  
Keyword(s):  
Genomic Imprinting ◽  
Dna Sequences ◽  
Nuclear Matrix ◽  
Regulatory Elements ◽  
Paternal Allele ◽  
Matrix Attachment Regions ◽  
Binding Assays ◽  
Allele Specific ◽  
Imprinting Control Region ◽  
Matrix Fraction

ABSTRACT Genomic imprinting at the Igf2/H19 locus originates from allele-specific DNA methylation, which modifies the affinity of some proteins for their target sequences. Here, we show that AT-rich DNA sequences located in the vicinity of previously characterized differentially methylated regions (DMRs) of the imprinted Igf2 gene are conserved between mouse and human. These sequences have all the characteristics of matrix attachment regions (MARs), which are known as versatile regulatory elements involved in chromatin structure and gene expression. Combining allele-specific nuclear matrix binding assays and real-time PCR quantification, we show that retention of two of these Igf2 MARs (MAR0 and MAR2) in the nuclear matrix fraction depends on the tissue and is specific to the paternal allele. Furthermore, on this allele, the Igf2 MAR2 is functionally linked to the neighboring DMR2 while, on the maternal allele, it is controlled by the imprinting-control region. Our work clearly demonstrates that genomic imprinting controls matrix attachment regions in the Igf2 gene.

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.

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