Comparative analyses of CTCF and BORIS occupancies uncover two distinct classes of CTCF binding genomic regions
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ABSTRACT:
PROVIDER: PRJNA289515 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2096740.fastq.gz | Fastqsanger.gz | |||
| SRR2096750.fastq.gz | Fastqsanger.gz | |||
| SRR2096760.fastq.gz | Fastqsanger.gz | |||
| SRR2096770.fastq.gz | Fastqsanger.gz | |||
| SRR2096741.fastq.gz | Fastqsanger.gz |
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Project description:CTCF and BORIS (CTCFL), two paralogous mammalian proteins sharing nearly identical DNA binding domains, are thought to function in mutually exclusive manners in DNA binding and transcriptional regulation. Here we show that these two proteins co-occupy a specific subset of regulatory elements consisting of clustered CTCF binding motifs (termed 2xCTSes). BORIS occupancy at 2xCTSes is largely invariant in BORIS-positive cancer cells, with the genomic pattern recapitulating the germline-specific BORIS binding to chromatin. In contrast to the single-motif CTCF target sites (1xCTSes), the 2xCTS elements are preferentially found at active promoters and enhancers, both in cancer and germ cells. 2xCTSes are also enriched in genomic regions that escape histone to protamine replacement in human and mouse sperm. Depletion of BORIS gene leads to altered transcription of a large number of genes and the differentiation of K562 cells, while the ectopic expression of this CTCF paralog leads to specific changes in transcription in MCF7 cells. In summary, we discover two functionally and structurally different classes of CTCF binding regions, 2xCTSes and 1xCTSes, revealed by their predisposition to bind BORIS. We propose that 2xCTSes play key roles in the transcriptional program of cancer and germ cells Genome-wide mapping of CTCF and BORIS occupancies in both germ and cancer cells. ChIP-seq and expression profiling by high throughput sequencing
2015-07-23 | E-GEOD-70764 | biostudies-arrayexpress
Project description:CTCF and BORIS (CTCFL), two paralogous mammalian proteins sharing nearly identical DNA binding domains, are thought to function in mutually exclusive manners in DNA binding and transcriptional regulation. Here we show that these two proteins co-occupy a specific subset of regulatory elements consisting of clustered CTCF binding motifs (termed 2xCTSes). BORIS occupancy at 2xCTSes is largely invariant in BORIS-positive cancer cells, with the genomic pattern recapitulating the germline-specific BORIS binding to chromatin. In contrast to the single-motif CTCF target sites (1xCTSes), the 2xCTS elements are preferentially found at active promoters and enhancers, both in cancer and germ cells. 2xCTSes are also enriched in genomic regions that escape histone to protamine replacement in human and mouse sperm. Depletion of BORIS gene leads to altered transcription of a large number of genes and the differentiation of K562 cells, while the ectopic expression of this CTCF paralog leads to specific changes in transcription in MCF7 cells. In summary, we discover two functionally and structurally different classes of CTCF binding regions, 2xCTSes and 1xCTSes, revealed by their predisposition to bind BORIS. We propose that 2xCTSes play key roles in the transcriptional program of cancer and germ cells
2015-07-23 | GSE70764 | GEO
Project description:BackgroundCTCF and BORIS (CTCFL), two paralogous mammalian proteins sharing nearly identical DNA binding domains, are thought to function in a mutually exclusive manner in DNA binding and transcriptional regulation.ResultsHere we show that these two proteins co-occupy a specific subset of regulatory elements consisting of clustered CTCF binding motifs (termed 2xCTSes). BORIS occupancy at 2xCTSes is largely invariant in BORIS-positive cancer cells, with the genomic pattern recapitulating the germline-specific BORIS binding to chromatin. In contrast to the single-motif CTCF target sites (1xCTSes), the 2xCTS elements are preferentially found at active promoters and enhancers, both in cancer and germ cells. 2xCTSes are also enriched in genomic regions that escape histone to protamine replacement in human and mouse sperm. Depletion of the BORIS gene leads to altered transcription of a large number of genes and the differentiation of K562 cells, while the ectopic expression of this CTCF paralog leads to specific changes in transcription in MCF7 cells.ConclusionsWe discover two functionally and structurally different classes of CTCF binding regions, 2xCTSes and 1xCTSes, revealed by their predisposition to bind BORIS. We propose that 2xCTSes play key roles in the transcriptional program of cancer and germ cells.
| S-EPMC4562119 | biostudies-literature
Project description:A common aberration in cancer is the activation of germline-specific proteins. The DNA-binding proteins among them generate novel chromatin states, not found in normal cells. The chromatin architecture protein CTCF has a germline-specific paralog BORIS/CTCFL, which is often erroneously activated in cancers. Another common feature of malignancies is the changed expression and epigenetic states of genomic repeats. The investigation of BORIS and CTCF binding to DNA repeats in cancer cell lines by ChIP-chip revealed three classes: elements cohabited by BORIS and CTCF, CTCF-bound only, or BORIS-only.
2016-08-17 | GSE84326 | GEO
Project description:CTCF is a key organizer of the 3D genome. Its specialized paralog, BORIS, heterodimerizes with CTCF but is expressed only in male germ cells and in cancer states. Unexpectedly, BORIS-null mice have only minimal germ cell defects. To understand the CTCF-BORIS relationship, mouse models with varied CTCF and BORIS levels were generated. Whereas Ctcf+/+Boris+/+, Ctcf+/-Boris+/+, and Ctcf+/+Boris-/- males are fertile, Ctcf+/-Boris-/- (Compound Mutant; CM) males are sterile. Testes with combined depletion of both CTCF and BORIS show reduced size, defective meiotic recombination, increased apoptosis, and malformed spermatozoa. Although CM germ cells exhibit only 25% of CTCF WT expression, chromatin binding of CTCF is preferentially lost from CTCF-BORIS heterodimeric sites. Furthermore, CM testes lose the expression of a large number of spermatogenesis genes and gain the expression of developmentally inappropriate genes that are “toxic” to fertility. Thus, a combined action of CTCF and BORIS is required to both repress pre-meiotic genes and activate post-meiotic genes for a complete spermatogenesis program.
2021-04-22 | GSE154249 | GEO
Project description:Pervasive usage of alternative promoters leads to deregulation of gene expression in carcinogenesis and may drive the emergence of new genes in spermatogenesis. However, little is known regarding the mechanisms underpinning the activation of alternative promoters. In our present study, we uncovered a novel mechanism by which alternative cancer-testis-specific transcription is activated from the intergenic and intronic clustered CTCF binding sites, which are transcriptionally inert in normal somatic cells. BORIS/CTCFL, a paralog of CTCF with cancer-testis-specific expression forms a heterodimer with CTCF at the clustered binding sites thus triggering epigenetic reprogramming of these sites into units of active transcription. BORIS binding to CTCF sites leads to the recruitment of chromatin-remodeling factor SRCAP, with subsequent replacement of H2A histone with H2A.Z, therefore creating a more relaxed chromatin state in the nucleosomes flanking the clustered binding sites. This facilitates opening of chromatin beyond CTCF/BORIS binding sites and paves the way to the recruitment of multiple additional transcription factors, thereby activating transcription from a given binding site. We demonstrate that the CTCF binding sites, epigenetically reprogrammed by ectopic BORIS expression can drive the expression of cancer-testis genes, long-noncoding RNAs, retro-pseudogenes, and dormant transposable elements harbored by activated long transcripts. Taking together, our results reveal that BORIS functions as a transcription factor that epigenetically reprograms clustered CTCF binding sites into transcriptional start sites, promoting transcription from alternative promoters in both germ cells and cancer cells.
2024-01-03 | GSE207058 | GEO
Project description:High-grade serous carcinoma (HGSC) is the most aggressive and predominant form of epithelial ovarian cancer and the leading cause of gynecological cancer death. We have previously shown that CTCFL (also known as BORIS, Brother of the Regulator of Imprinted Sites) is expressed in a large proportion of ovarian cancers, which is associated with global and promoter-specific DNA hypomethylation, advanced tumor stage, and poor prognosis. To explore its functional role in HGSC, we expressed BORIS in human fallopian tube secretory epithelial cells (FTSEC), the presumptive cell of origin for HGSC. BORIS-expressing cells exhibited increased motility and invasion, and BORIS expression was associated with alterations in several cancer-associated gene expression networks, including fatty acid metabolism, TNF signaling, cell migration, and ECM-receptor interactions. Importantly, GALNT14, a glycosyltransferase gene previously implicated in cancer cell migration and invasion, was highly induced by BORIS, and GALNT14 knockdown significantly abrogated BORIS-induced cell motility and invasion. In addition, in silico analyses provided evidence for BORIS and GALNT14 co-expression in several human cancers. Finally, ChIP-seq demonstrated that expression of BORIS in FTSEC cells was associated with de novo and enhanced binding of CTCF at hundreds of loci, many of which correlated with activation of transcription at target genes, including GALNT14. Taken together, our data indicate that BORIS may promote cell motility and invasion in HGSC via upregulation of GALNT14, and suggests BORIS as a potential therapeutic target in this malignancy.
2019-07-01 | GSE131931 | GEO
Project description:Brother of Regulator of Imprinted Sites (BORIS) is a DNA binding protein with high similarity to CCCTC binding factor (CTCF), a multifunctional transcription factor that plays an important role in genome organization. Like CTCF, BORIS plays a role in transcriptional regulation. BORIS becomes aberrantly expressed in melanoma with a higher frequency in metastatic tumors compared to primary tumors, which indicates a role for BORIS in melanoma progression. Currently, little is known about the role of BORIS in melanoma. To gain insight into the functional role of BORIS in melanoma we established doxycycline-inducible BORIS expression in the MM057 melanoma cell line that harbors a proliferation-associated transcriptome. Next, we used RNA-seq to investigate BORIS-mediated transcriptional changes. We show that differentially expressed genes are enriched among invasion-related processes and gene signatures, indicating that BORIS expression contributes to an EMT-like switch from a proliferation to invasion-associated transcriptome. In agreement with these findings, we demonstrate that BORIS overexpression leads to reduced proliferation and increased migration and invasion. Taken together, these data indicate that expression of BORIS promotes a switch from a proliferative to invasive state at both the transcriptional and phenotypic level in melanoma cell lines.
2020-01-01 | GSE126807 | GEO
Project description:The study involved chromatin IP analyzed by high-throughput sequencing analysis using purifird germ cells from M. fascucularis testis M. fascicularis is a monkey with non-seasonal male germ cells production, and the most popular primate for preclinical animal studies. The goal of the study was to investigate the epigenome of M. fscicularis testis with respect to mei-Cohesin complexes, CTCF and BORIS
2022-09-30 | GSE118006 | GEO
Project description:To identify differentially expressed genes in Boris KO testis, gene expression profilings were performed with NIAID mouse customized arrays. Gene expressions of five biological replicates of Boris KO testis were compared to those of wild type testis. Total RNAs from WT and BORIS KO testes prepared from P14 mice were labelled with Cy5 and Cy3, respectively. Five sets of each genotype were studied.
2010-06-05 | E-GEOD-19162 | biostudies-arrayexpress