CTCF plays a key role in organizing chromatin into TAD structures but it can also function as a transcription factor. CTCFL (CTCF-like), the paralog of CTCF, is normally transiently expressed in pre-meiotic male germ cells together with ubiquitously expressed CTCF. It plays a unique role in spermatogenesis by regulating expression of testis-specific genes. Genetic alterations in CTCF and its paralog CTCFL have both been found in numerous cancers, but it remains unknown to what extent CTCFL deregulates transcription on its own or by opposing CTCF. Here, we discuss some of the potential mechanisms by which these two proteins could alter gene regulation and contribute to oncogenic transcriptional programs.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893514 | PMC |
http://dx.doi.org/10.1016/j.gde.2020.02.021 | DOI Listing |
ACS Omega
December 2024
Department of Urology, Suzhou Ninth Hospital affiliated to Soochow University, Suzhou 215000, China.
iScience
December 2024
Center for Comparative Biomedicine, Ministry of Education Key Laboratory of Systems Biomedicine, State Key Laboratory of Medical Genomics, Institute of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
As an essential regulator of higher-order chromatin structures, CCCTC-binding factor (CTCF) is a highly conserved protein with a central DNA-binding domain of 11 tandem zinc fingers (ZFs), which are flanked by amino (N-) and carboxy (C-) terminal domains of intrinsically disordered regions. Here we report that CRISPR deletion of the entire C-terminal domain of alternating charge blocks decreases CTCF DNA binding but deletion of the C-terminal fragment of 116 amino acids results in increased CTCF DNA binding and aberrant gene regulation. Through a series of genetic targeting experiments, in conjunction with electrophoretic mobility shift assay (EMSA), circularized chromosome conformation capture (4C), qPCR, chromatin immunoprecipitation with sequencing (ChIP-seq), and assay for transposase-accessible chromatin with sequencing (ATAC-seq), we uncovered a negatively charged region (NCR) responsible for weakening CTCF DNA binding and chromatin accessibility.
View Article and Find Full Text PDFCell Prolif
December 2024
State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
CTCF plays a vital role in shaping chromatin structure and regulating gene expression. Clinical studies have associated CTCF mutations with congenital developmental abnormalities, including congenital cardiomyopathy. In this study, we investigated the impact of the homozygous CTCF-R567W (Ctcf) mutation on cardiac tissue morphogenesis during mouse embryonic development.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
EED (embryonic ectoderm development) is a core subunit of the polycomb repressive complex 2 (PRC2), which senses the trimethylation of histone H3 lysine 27 (H3K27). However, its biological function in cerebellar development remains unknown. Here, we show that EED deletion from neural stem cells (NSCs) or cerebellar granule cell progenitors (GCPs) leads to reduced GCPs proliferation, cell death, cerebellar hypoplasia, and motor deficits in mice.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!