A5008093148- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Genetic Syndromes and Imprinting
- Cancer-related gene regulation
- Caveolin-1 and cellular processes
- RNA Research and Splicing
- Ovarian cancer diagnosis and treatment
- Cancer-related molecular mechanisms research
- Cancer Cells and Metastasis
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Prenatal Screening and Diagnostics
- Cancer, Hypoxia, and Metabolism
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Ferroptosis and cancer prognosis
- TGF-β signaling in diseases
- Cancer, Lipids, and Metabolism
- Genetics and Neurodevelopmental Disorders
- Telomeres, Telomerase, and Senescence
- Genetic factors in colorectal cancer
- Renal and related cancers
- RNA Interference and Gene Delivery
- Pancreatic function and diabetes
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
National Institute of Allergy and Infectious Diseases
2011-2024
National Institutes of Health
2010-2024
University Hospital of Lausanne
2007-2010
Universidad de Cantabria
2007
Institute for Molecular Medicine
2007
National Cancer Institute
2004
Science Applications International Corporation (United States)
2004
National Institute of Neurological Disorders and Stroke
2002
University of Essex
2002
Washington University in St. Louis
2002
The DNA-binding protein CCCTC-binding factor (CTCF) and the cohesin complex function together to shape chromatin architecture in mammalian cells, but molecular details of this process remain unclear. Here, we demonstrate that a 79-aa region within CTCF N terminus is essential for positioning at binding sites loop formation. However, fused artificial zinc fingers was not sufficient redirect non-CTCF sites, indicating lack an autonomously functioning domain responsible positioning. BORIS...
CTCF, a conserved, ubiquitous, and highly versatile 11-zinc-finger factor involved in various aspects of gene regulation, forms methylation-sensitive insulators that regulate X chromosome inactivation expression imprinted genes. We document here the existence paralogous with same exons encoding domain as mammalian CTCF genes thus DNA-binding potential, but distinct amino carboxy termini. named this BORIS for B rother o f R egulator I mprinted S ites. is present only testis, expressed...
The low density lipoprotein receptor-related protein (LRP) functions in the catabolism of numerous ligands including proteinases, proteinase inhibitor complexes, and lipoproteins. In current study we provide evidence indicating an expanded role for LRP modulating cellular signaling events. Our results show that platelet-derived growth factor (PDGF) BB induces a transient tyrosine phosphorylation cytoplasmic domain process dependent on PDGF receptor activation c-Src family kinase activity....
Brother of the Regulator Imprinted Sites (BORIS) is a mammalian CTCF paralog with same central 11Zn fingers (11ZF) that mediate specific interactions varying approximately 50-bp target sites. Regulated in vivo occupancy such sites may yield structurally and functionally distinct CTCF/DNA complexes involved various aspects gene regulation, including epigenetic control imprinting X chromosome inactivation. The latter functions are mediated by meCpG-sensitive 11ZF binding. Because normally...
Regulatory sequences recognized by the unique pair of paralogous factors, CTCF and BORIS, have been implicated in epigenetic regulation imprinting X chromosome inactivation. Lung cancers exhibit genome-wide demethylation associated with derepression a specific class genes encoding cancer-testis (CT) antigens such as NY-ESO-1. CT are normally expressed BORIS-positive male germ cells deficient meCpG contents, but strictly silenced somatic cells. The present study was undertaken to ascertain if...
Expression of hTERT is the major limiting factor for telomerase activity. We previously showed that methylation promoter necessary its transcription and CTCF can repress by binding to first exon. In this study, we used electrophoretic mobility shift assay (EMSA) chromatin immunoprecipitation (ChIP) show does not bind methylated exon hTERT. Treatment telomerase-positive cells with 5-azadC led a strong demethylation 5′-regulatory region, reactivation downregulation Although complete was...
CTCF is a transcription factor with highly versatile functions ranging from gene activation and repression to the regulation of insulator function imprinting. Although many these rely on CTCF-DNA interactions, it an emerging realization that CTCF-dependent molecular processes involve interactions other proteins. In this study, we report association subpopulation RNA polymerase II (Pol II) protein complex. We identified largest subunit Pol (LS as significantly colocalizing in nucleus...
CTCF and BORIS (CTCFL), two paralogous mammalian proteins sharing nearly identical DNA binding domains, are thought to function in a mutually exclusive manner transcriptional regulation. Here we show that these co-occupy specific subset of regulatory elements consisting clustered motifs (termed 2xCTSes). occupancy at 2xCTSes is largely invariant BORIS-positive cancer cells, with the genomic pattern recapitulating germline-specific chromatin. In contrast single-motif target sites (1xCTSes),...
BORIS, like other members of the 'cancer/testis antigen' family, is normally expressed in testicular germ cells and repressed somatic cells, but aberrantly activated cancers. To understand regulatory mechanisms governing human BORIS expression, we characterized its 5'-flanking region. Using 5' RACE, identified three promoters, designated A, B C, corresponding to transcription start sites at -1447, -899 -658 bp upstream first ATG. Alternative promoter usage generated least five alternatively...
The choice mechanisms that determine the future inactive X chromosome in somatic cells of female mammals involve regulated expression XIST gene. A familial C(-43)G mutation promoter results skewing inactivation (XCI) towards heterozygous females, whereas a C(-43)A found primarily active opposite pattern. Both mutations point to existence factor might be responsible for skewed patterns. Here we identify this as CTCF, conserved protein with 11 Zn-finger (ZF) domain can mediate multiple...
CTCF is a widely expressed and highly conserved multi-Zn-finger (ZF) nuclear factor. Binding to various target sites (CTSs) mediated by combinatorial contributions of different ZFs. Different CTSs mediate distinct functions in transcriptional regulation, including promoter repression or activation hormone-responsive gene silencing. In addition, the necessary sufficient core sequences diverse enhancer-blocking (insulator) elements, CpG methylation-sensitive ones, have recently been pinpointed...
Imprinted methylation of the paternal Rasgrf1 allele in mice occurs at a differentially methylated domain (DMD) 30 kbp 5′ promoter. A repeated sequence 3′ DMD regulates imprinted methylation, which is required for expression. Here we identify mechanism by controls imprinting. The an enhancer blocker that binds CTCF methylation-sensitive manner. bound to unmethylated maternal silences binding prevented repeat-mediated allowing Optimal vitro enhancer-blocking activity requires sites. can be...
Previously, it was shown that the CTCF paralogous gene, BORIS (brother of regulator imprinted sites) is expressed in male germ cells, but its function spermatogenesis has not been defined. To develop an understanding functional activities BORIS, we generated knockout (KO) mice. Mice homozygous for null allele had a defect resulted small testes associated with increased cell death. The evident as early postnatal day 21 and manifested by delayed production haploid cells. By gene expression...
Telomerase activity, not detectable in somatic cells but frequently activated during carcinogenesis, confers immortality to tumors. Mechanisms governing expression of the catalytic subunit hTERT , limiting factor for telomerase still remain unclear. We previously proposed a model which binding transcription CTCF two first exons results transcriptional inhibition normal cells. This is abrogated, however, by methylation sites 85% Here, we showed that was unmethylated testicular and ovarian...
The role of repetitive DNA sequences in pericentromeric regions with respect to kinetochore/heterochromatin structure and function is poorly understood. Here, we use a mouse erythroleukemia cell (MEL) system for studying how assumes or assembled into different chromatin structures. We show that human gamma-satellite arrays allow transcriptionally permissive conformation an adjacent transgene efficiently protect it from epigenetic silencing. These contain CTCF Ikaros binding sites. In MEL...
Cancer/testis (CT) genes predominantly expressed in the testis (germ cells) and generally not other normal tissues are aberrantly human cancers. This highly restricted expression provides a unique opportunity to use these CT for diagnostics, immunotherapeutic, or targeted therapies. The purpose of this study was identify those with greatest incidence uterine cancers.We queried known putative gene transcripts (representing 79 loci) using whole genome arrays. Specifically, global expressions...
Background BORIS/CTCFL is a paralogue of CTCF, the major epigenetic regulator vertebrate genomes. BORIS normally expressed only in germ cells but aberrantly activated numerous cancers. While recent studies demonstrated that transcriptional activator testis-specific genes, little generally known about its biological and molecular functions. Methodology/Principal Findings Here we show as 23 isoforms germline cancer cells. The are comprised alternative N- C-termini combined with varying numbers...
Abstract Background Pervasive usage of alternative promoters leads to the deregulation gene expression in carcinogenesis and may drive emergence new genes spermatogenesis. However, little is known regarding mechanisms underpinning activation promoters. Results Here we describe how cancer-testis-specific transcription activated. We show that intergenic intronic CTCF binding sites, which are transcriptionally inert normal somatic cells, could be epigenetically reprogrammed into active de novo...