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Series GSE207058 Query DataSets for GSE207058
Status Public on Jan 03, 2024
Title BORIS/CTCFL epigenetically reprograms clustered CTCF binding sites into alternative transcriptional start sites.
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary 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.
 
Overall design Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for two paralogous proteins, CTCF and BORIS (CTCFL), in combination with gene expression profiling analysis by RNA-seq and mapping of epigenetic marks by ChIP-seq.
Web link https://genomebiology.biomedcentral.com/articles/10.1186/s13059-024-03175-0#:~:text=CTCF%20divides%20genomes%20into%20topologically,34%2C35%2C36%5D.
 
Contributor(s) Pugacheva EM
Citation(s) 38297316
Submission date Jun 27, 2022
Last update date Feb 02, 2024
Contact name Elena Pugacheva
E-mail(s) epugacheva@niaid.nih.gov
Phone 2407377366
Organization name NIH
Department NIAID
Lab LIG
Street address Bldg.29B
City Bethesda
State/province MD
ZIP/Postal code 20814
Country USA
 
Platforms (5)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL21626 NextSeq 550 (Mus musculus)
Samples (140)
GSM6276497 ChIP-seq with H2AZ Abs in MCF7+EV cells
GSM6276498 ChIP-seq with H2AZ Abs in MCF7+BORIS cells
GSM6276499 ChIP-seq with H2AZ Abs in MDA-MB-435+EV cells
Relations
BioProject PRJNA853953

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE207058_RAW.tar 45.0 Gb (http)(custom) TAR (of BEDGRAPH, BIGWIG, WIG, XLSX)
GSE207058_RNA_Seq_293T_BORIS_Clone1.xlsx 1.5 Mb (ftp)(http) XLSX
GSE207058_RNA_Seq_K562_WTvs_Clone7_BORISdepleted.xlsx 17.7 Mb (ftp)(http) XLSX
GSE207058_RNA_Seq_MDA_MB_435_BORIS_Clone1.xlsx 37.3 Mb (ftp)(http) XLSX
GSE207058_RNAseq_FPKM.xlsx 3.9 Mb (ftp)(http) XLSX
GSE207058_RNAseq_pBIG_Dox_100bp_NGS.xlsx 2.2 Mb (ftp)(http) XLSX
GSE207058_RNAseq_pBIG_Dox_50bp_NGS.xlsx 2.5 Mb (ftp)(http) XLSX
GSE207058_RNAseq_siRNAs_H2AZ_pBIG.xlsx 3.2 Mb (ftp)(http) XLSX
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Processed data provided as supplementary file
Processed data are available on Series record
Raw data are available in SRA

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