DNA methylation in the CTCF-binding site I and the expression pattern of theH19 gene: Does positive expression predict poor prognosis in early stage head and neck carcinomas?

2005 ◽  
Vol 44 (2) ◽  
pp. 102-110 ◽  
Author(s):  
Leda I.C.V. Esteves ◽  
Afonso C. Javaroni ◽  
Inês N. Nishimoto ◽  
José Magrin ◽  
Jeremy A. Squire ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Head And Neck ◽  
Binding Site ◽  
Expression Pattern ◽  
Poor Prognosis ◽  
Early Stage ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Head And Neck Carcinomas ◽  
Positive Expression

scholarly journals 3'HS1 CTCF binding site in human β-globin locus regulates fetal hemoglobin expression

2021 ◽  
Author(s):  
Pamela Himadewi ◽  
Xue Qing David Wang ◽  
Fan Feng ◽  
Haley Gore ◽  
Yushuai Liu ◽  
...  
Keyword(s):  
Binding Site ◽  
Progenitor Cells ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Distal Enhancer ◽  
Erythroid Progenitor ◽  
Hematopoietic Stem ◽  
Ctcf Site

Mutations in the adult β-globin gene can lead to a variety of hemoglobinopathies, including sickle cell disease and β-thalassemia. An increase in fetal hemoglobin expression throughout adulthood, a condition named Hereditary Persistence of Fetal Hemoglobin (HPFH), has been found to ameliorate hemoglobinopathies. Deletional HPFH occurs through the excision of a significant portion of the 3 prime end of the β-globin locus, including a CTCF binding site termed 3'HS1. Here, we show that the deletion of this CTCF site alone induces fetal hemoglobin expression in both adult CD34+ hematopoietic stem and progenitor cells and HUDEP-2 erythroid progenitor cells. This induction is driven by the ectopic access of a previously postulated distal enhancer located in the OR52A1 gene downstream of the locus, which can also be insulated by the inversion of the 3'HS1 CTCF site. This suggests that genetic editing of this binding site can have therapeutic implications to treat hemoglobinopathies.

Allele-specific methylation of a functional CTCF binding site upstream of MEG3 in the human imprinted domain of 14q32

2005 ◽  
Vol 13 (8) ◽  
pp. 809-818 ◽  
Author(s):  
Alberto L. Rosa ◽  
Yuan-Qing Wu ◽  
Bernard Kwabi-Addo ◽  
Karen J. Coveler ◽  
V. Reid Sutton ◽  
...  
Keyword(s):  
Binding Site ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Allele Specific ◽  
Allele Specific Methylation

scholarly journals CTCFBSDB: a CTCF-binding site database for characterization of vertebrate genomic insulators

2007 ◽  
Vol 36 (Database) ◽  
pp. D83-D87 ◽  
Author(s):  
L. Bao ◽  
M. Zhou ◽  
Y. Cui
Keyword(s):  
Binding Site ◽  
Ctcf Binding ◽  
Ctcf Binding Site

scholarly journals HTLV-1 inserts an ectopic CTCF-binding site into the human genome

Retrovirology ◽  
2015 ◽  
Vol 12 (S1) ◽  
Author(s):  
Yorifumi Satou ◽  
Miyazato Paola ◽  
Ko Ishihara ◽  
Asami Fukuda ◽  
Kisato Nosaka ◽  
...  
Keyword(s):  
Binding Site ◽  
Human Genome ◽  
Ctcf Binding ◽  
Ctcf Binding Site

210 DNA METHYLATION AND HYDROXYMETHYLATION ANALYSIS IN A MODEL OF OOCYTE DIFFERENTIAL DEVELOPMENTAL COMPETENCE IN SHEEP

2015 ◽  
Vol 27 (1) ◽  
pp. 195
Author(s):  
L. Masala ◽  
D. Bebbere ◽  
G. P. Burrai ◽  
F. Ariu ◽  
L. Bogliolo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Embryo Development ◽  
Oocyte Quality ◽  
Developmental Competence ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Global Methylation ◽  
Tet Genes ◽  
Lower Expression

DNA methylation is an important epigenetic mark that plays a role in gene regulation by the addition of a methyl group to CpG islands in the DNA. Despite being relatively stable in somatic cells, DNA methylation is subject to reprogramming during embryo development and gametogenesis. The aim of this work was to evaluate different aspects of DNA methylation in relation to oocyte quality in the ovine species. A model of differential developmental competence consisting in ovine oocytes and in vitro produced (IVP) blastocysts derived from adult (AD) and prepubertal (PR) donors, was used. The methylation was analysed in terms of: expression of a panel of genes involved in DNA methylation [DNA methyltransferases (DNMTs)] and demethylation [ten-eleven translocation dioxygenases (TET)] in oocytes and blastocysts; global methylation and hydroxymethylation by direct immunofluorescence; locus-specific methylation of 2 imprinted genes by pyrosequencing. Gene relative quantification was performed by RNA reverse transcription followed by real-time PCR. Pools of 10 immature (GV) and in vitro-matured (MII) oocytes and (IVP) blastocysts derived from AD and PR donors (4 replicates per class) were analysed. Lower expression of TET1, TET2, and TET3 was observed in PR GV oocytes (ANOVA; P < 0.05), while no significant differences were found for the enzymes involved in methylation (DNMT1, DNMT3A, DNMT3B; ANOVA; P > 0.05). The levels of all the genes studied showed no significant differences in embryos at blastocyst stage (ANOVA; P > 0.05). Methylation and hydroxymethylation immunostaining were performed in GV and MII oocytes using anti-5-methylcytosine mouse mAb and 5-hydroxymethylcytosine rabbit pAB. High levels of DNA methylation were observed in both AD and PR GV and MII oocytes, while hydroxymethylation immunopositivity was scattered evident throughout the gamete chromatin. Pyrosequencing of bisulfite converted DNA was used to determine the methylation status within differentially methylated regions (DMR) of maternally imprinted H19 (CTCF binding site IV; 11 CpG sites) and paternally imprinted IGF2R (17CpG sites within intron 2). No differences were observed between classes of oocytes for each gene (pools of 40 oocytes per replicate, 3 replicates per class; ANOVA; P > 0.05). Our work shows no differences in the expression of the enzymes involved in methylation, in accordance with the results of global and locus specific methylation analysis. Conversely, we observed lower expression of the TET genes in PR GV oocytes (ANOVA; P > 0.05). TET1, TET2, and TET3, whose expression has never been studied in ovine, generate 5-hydroxymethlcytosine (5hmC) by oxidation of 5-methylcytosine (5mC), and are involved in active DNA demethylation during early embryo development. Our observation of lower expression of the TET genes in lower competence PR GV oocytes suggests that epigenetic mechanisms may affect oocyte quality and paves the way to better understand methylation dynamics during sheep pre-implantation development.

scholarly journals An exceptionally conserved transcriptional repressor, CTCF, employs different combinations of zinc fingers to bind diverged promoter sequences of avian and mammalian c-myc oncogenes.

1996 ◽  
Vol 16 (6) ◽  
pp. 2802-2813 ◽  
Author(s):  
G N Filippova ◽  
S Fagerlie ◽  
E M Klenova ◽  
C Myers ◽  
Y Dehner ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Site ◽  
Expression Patterns ◽  
Transcriptional Repressor ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Cdna Clones ◽  
Regulatory Sequences ◽  
P2 Promoter ◽  
Gel Shift

We have isolated and analyzed human CTCF cDNA clones and show here that the ubiquitously expressed 11-zinc-finger factor CTCF is an exceptionally highly conserved protein displaying 93% identity between avian and human amino acid sequences. It binds specifically to regulatory sequences in the promoter-proximal regions of chicken, mouse, and human c-myc oncogenes. CTCF contains two transcription repressor domains transferable to a heterologous DNA binding domain. One CTCF binding site, conserved in mouse and human c-myc genes, is found immediately downstream of the major P2 promoter at a sequence which maps precisely within the region of RNA polymerase II pausing and release. Gel shift assays of nuclear extracts from mouse and human cells show that CTCF is the predominant factor binding to this sequence. Mutational analysis of the P2-proximal CTCF binding site and transient-cotransfection experiments demonstrate that CTCF is a transcriptional repressor of the human c-myc gene. Although there is 100% sequence identity in the DNA binding domains of the avian and human CTCF proteins, the regulatory sequences recognized by CTCF in chicken and human c-myc promoters are clearly diverged. Mutating the contact nucleotides confirms that CTCF binding to the human c-myc P2 promoter requires a number of unique contact DNA bases that are absent in the chicken c-myc CTCF binding site. Moreover, proteolytic-protection assays indicate that several more CTCF Zn fingers are involved in contacting the human CTCF binding site than the chicken site. Gel shift assays utilizing successively deleted Zn finger domains indicate that CTCF Zn fingers 2 to 7 are involved in binding to the chicken c-myc promoter, while fingers 3 to 11 mediate CTCF binding to the human promoter. This flexibility in Zn finger usage reveals CTCF to be a unique "multivalent" transcriptional factor and provides the first feasible explanation of how certain homologous genes (i.e., c-myc) of different vertebrate species are regulated by the same factor and maintain similar expression patterns despite significant promoter sequence divergence.

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