Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
CTCF plays key roles in gene regulation, chromatin insulation, imprinting, X chromosome inactivation and organizing the higher-order chromatin architecture of mammalian genomes. Previous studies have mainly focused on the roles of the canonical CTCF isoform. Here, we explore the functions of an alternatively spliced human CTCF isoform in which exons 3 and 4 are skipped, producing a shorter isoform (CTCF-s). Functionally, we find that CTCF-s competes with the genome binding of canonical CTCF and binds a similar DNA sequence. CTCF-s binding disrupts CTCF/cohesin binding, alters CTCF-mediated chromatin looping and promotes the activation of IFI6 that leads to apoptosis. This effect is caused by an abnormal long-range interaction at the IFI6 enhancer and promoter. Taken together, this study reveals a non-canonical function for CTCF-s that antagonizes the genomic binding of canonical CTCF and cohesin, and that modulates chromatin looping and causes apoptosis by stimulating IFI6 expression.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449404 | PMC |
| http://dx.doi.org/10.1038/s41467-019-08949-w | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Positional distribution of transcription factor binding sites in the human genome.
PLoS One
July 2025
Biodiversity Research Center, Academia Sinica, Taipei, Taiwan.
As transcription factors (TFs) play a major role in gene regulation, we studied their binding motifs (positional weight matrices, PWMs) and binding sites (TFBSs) in the human genome, and how TFs bind DNA motifs, including the involvement of binding co-factors. Using the chromatin immunoprecipitation sequencing data recently released by ENCODE (Encyclopedia of DNA Elements), we obtained new PWMs for 196 TFs and revised PWMs for 119 TFs. From these and the PWMs previously obtained for 235 TFs, we inferred the canonical PWMs for 500 TFs, including 243 new PWMs.
View Article and Find Full Text PDFSenescence-Associated Chromatin Rewiring Promotes Inflammation and Transposable Element Activation.
bioRxiv
June 2025
Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA.
Cellular senescence is a stable form of cell cycle arrest that contributes to aging and age-associated diseases through the secretion of inflammatory factors collectively known as the senescence-associated secretory phenotype (SASP). While senescence is driven by transcriptional and epigenetic changes, the contribution of higher-order genome organization remains poorly defined. Here, we present the highest-resolution Hi-C maps (~3 kb) to date of proliferating, quiescent, and replicative senescent (RS) human fibroblasts, enabling a comprehensive analysis of 3D genome architecture during senescence.
View Article and Find Full Text PDFMotif distribution and DNA methylation underlie distinct Cdx2 binding during development and homeostasis.
Nat Commun
January 2025
Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Transcription factors guide tissue development by binding to developmental stage-specific targets and establishing an appropriate enhancer landscape. In turn, DNA and chromatin modifications direct the genomic binding of transcription factors. However, how transcription factors navigate chromatin features to selectively bind a small subset of all the possible genomic target loci remains poorly understood.
View Article and Find Full Text PDFPRC1 and CTCF-Mediated Transition from Poised to Active Chromatin Loops Drives Bivalent Gene Activation.
bioRxiv
November 2024
Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, PA 17033.
Polycomb Repressive Complex 1 (PRC1) and CCCTC-binding factor (CTCF) are critical regulators of 3D chromatin architecture that influence cellular transcriptional programs. Spatial chromatin structures comprise conserved compartments, topologically associating domains (TADs), and dynamic, cell-type-specific chromatin loops. Although the role of CTCF in chromatin organization is well-known, the involvement of PRC1 is less understood.
View Article and Find Full Text PDFA Compendium of G-Flipon Biological Functions That Have Experimental Validation.
Int J Mol Sci
September 2024
Discovery, InsideOutBio, 42 8th Street, Unit 3412, Charlestown, MA 02129, USA.
Article Synopsis
- Research on G-quadruplexes (GQs) reveals complex and unexpected results regarding their biological roles, especially in genome maintenance and transcription.
- GQs are formed from repeat sequences, particularly the (GN)G motif, which is evolutionarily favored in birds and mammals.
- The interaction between GQs, noncoding RNAs, and transcription factors indicates a deep evolutionary connection, impacting processes like cell fate specification during embryonic development.