Effect of BORIS depletion on transcriptome of breast cancer cell line MCF7
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE81001 | GEO | 2017/09/25
SECONDARY ACCESSION(S): PRJNA320262
REPOSITORIES: GEO
Similar Datasets
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:This study compares the transcripts bound to BORIS in neural progenitor cells and cells differentiated for 6 days into young neurons We present expression profiles for neural progenitor cells (arrays hybridised in triplicate) and in young neurons (arrays hybridised in duplicate). Immunoprecipitated BORIS-mRNA complexes were used to assess the association of BORIS with target mRNAs in neural progenitor cells and in young neurons (both arrays hybridised in duplicate).
2013-11-29 | E-GEOD-42294 | biostudies-arrayexpress
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
Project description:Alternative splicing of pre-mRNA is a prominent mechanism to generate protein diversity, yet its regulation is poorly understood. Here, we demonstrate a direct role for histone modifications in alternative splicing. We find distinctive histone modification signatures which correlate with splicing outcome in a set of human genes. Modulation of histone modifications causes splice site switching. The mechanism for histone-mediated splice site selection involves a histone mark which is read by a chromatin protein, which in turn recruits a splicing regulator. These results outline an adaptor system for reading of histone marks by the pre-mRNA splicing machinery. To obtain an estimate of how many PTB-dependent alternative splicing events are regulated by SET2/MRG15-mediated recruitment of PTB, we carried out a genomewide comparative analysis of alternative splicing in hMSC cells depleted of either SETD2, MRG15 or PTB using specific siRNAs, or mock-depleted using a control siRNA.
2010-02-10 | E-GEOD-19373 | biostudies-arrayexpress
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: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:BORIS expresses abnormally in colorectal cancer cells. Both the expression and the copy number of BORIS are remarkably higher in colorectal cancer cells than in normal colon or rectal cells. BORIS is potential diagnosis, prognosis or therapeutic target for colorectal cancer. To expand our view of the signaling pathway related with BORIS, altered gene expression by BORIS knockdown was assessed by microarray assay. To study the gene regulation by BORIS knockdown, microarray assay was applied to screen the gene expression regulated by BORIS siRNA in colorectal cancer cells HCT116 and Caco-2
2018-07-01 | GSE86172 | GEO
Project description:Splicing of precursor mRNA (pre-mRNA) is an important regulatory step in gene expression. Recent evidence points to a regulatory role of chromatin-related proteins in alternative splicing (AS) regulation. Using an unbiased approach, we have identified the acetyltransferase p300 as a key chromatin-related regulator of AS. P300 promotes genome-wide exon inclusion in both a transcription-dependent and ‑independent manner. Using CD44 as a paradigm, we found that p300 regulates AS by modulating the binding of splicing factors to pre-mRNA. Employing a tethering strategy, we found that binding of p300 to the CD44 promoter region promotes CD44v exon inclusion independently of RNAPII transcriptional elongation rate. Promoter-bound p300 regulates AS by acetylating splicing factors, leading to exclusion of hnRNP M from CD44 pre-mRNA and activation of Sam68. P300-mediated CD44 AS reduces cell motility and promotes epithelial features. Our findings reveal a mechanism through which chromatin-related proteins regulate AS and show the impact of this mechanism on cell function.
2019-10-31 | GSE109957 | 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.
2010-03-31 | GSE19162 | GEO