scholarly journals Loss of imprinting of IGF2 and H19 in osteosarcoma is accompanied by reciprocal methylation changes of a CTCF-binding site

2003 ◽  
Vol 12 (5) ◽  
pp. 535-549 ◽  
Author(s):  
G. A. Ulaner
Keyword(s):  
Binding Site ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Loss Of Imprinting

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

scholarly journals Loss of imprinting control of the lncRNA H19-fetal mitogen IGF2 gene cluster in the decidual microenvironment of patients with idiopathic spontaneous miscarriages

2021 ◽  
Author(s):  
Xue Wen ◽  
Qi Zhang ◽  
Lei Zhou ◽  
Zhaozhi Li ◽  
Xue Wei ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Noncoding Rna ◽  
Recurrent Miscarriage ◽  
Critical Role ◽  
Ctcf Binding ◽  
Ctcf Binding Site ◽  
Monoallelic Expression ◽  
Endometrial Stromal Cells ◽  
Control Center ◽  
Loss Of Imprinting

Abstract Miscarriage, the spontaneous loss of a pregnancy before the fetus achieves viability, is a common complication of pregnancy. Decidualization plays a critical role in the implantation of the embryo. To search for molecular factors underlying miscarriage, we explored the role of long noncoding RNAs (lncRNAs) in the decidual microenvironment, where the molecular crosstalk at the feto–maternal interface occurs. By integrating RNA-seq data from recurrent miscarriage patients and decidualized endometrial stromal cells, we identified H19 , a noncoding RNA that exhibits paternally imprinted monoallelic expression in normal tissues, as the most upregulated lncRNA associated with miscarriage. Aberrant upregulation of H19 lncRNA was observed in decidual tissues derived from patients with spontaneous miscarriage as well as decidualized endometrial stromal cells. The maternally imprinted fetal mitogen Igf2, which is usually reciprocally co-regulated with H19 in the same imprinting cluster, was also upregulated. Notably, both genes underwent loss of imprinting, as H19 and IGF2 were actively transcribed from both parental alleles in decidual tissues. Mechanistically, this loss of imprinting in decidual tissues was associated with the loss of the H3K27m3 suppression marker in the IGF2 promoter, CpG hypomethylation at the central CTCF binding site in the imprinting control center (ICR) that is located between IGF2 and H19 , and the loss of CTCF-mediated intrachromosomal looping. These data provide the first evidence that aberrant control of the ICR epigenotype-intrachromosomal looping- H19/IGF2 imprinting pathway may be a critical epigenetic risk factor in the abnormal decidualization related to miscarriage.

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.

scholarly journals Loop competition and extrusion model predicts CTCF interaction specificity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wang Xi ◽  
Michael A. Beer
Keyword(s):  
Binding Site ◽  
Critical Role ◽  
Three Dimensional ◽  
Ctcf Binding ◽  
Chromatin Interaction ◽  
Ctcf Binding Site ◽  
Loop Formation ◽  
Critical Determinant ◽  
Frequency Changes ◽  
Transcriptional Gene Regulation

AbstractThree-dimensional chromatin looping interactions play an important role in constraining enhancer–promoter interactions and mediating transcriptional gene regulation. CTCF is thought to play a critical role in the formation of these loops, but the specificity of which CTCF binding events form loops and which do not is difficult to predict. Loops often have convergent CTCF binding site motif orientation, but this constraint alone is only weakly predictive of genome-wide interaction data. Here we present an easily interpretable and simple mathematical model of CTCF mediated loop formation which is consistent with Cohesin extrusion and can predict ChIA-PET CTCF looping interaction measurements with high accuracy. Competition between overlapping loops is a critical determinant of loop specificity. We show that this model is consistent with observed chromatin interaction frequency changes induced by CTCF binding site deletion, inversion, and mutation, and is also consistent with observed constraints on validated enhancer–promoter interactions.

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