CTCF as a multivalent eukaryotic transcription factor plays a diverse range of roles in regulation of various genes through the binding of its 11 zinc fingers to CTCF consensus sites or various proteins. CTCF is involved in multiple aspects of epigenetic regulation including regulation of chromatin remodeling and genomic imprinting. Deregulation of these processes result in a group of diseases are characterized by growth, development, and neurological dysfunction. This paper reviews recent researches that highlight the links between CTCF, epigenetics and diseases.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2012.02.013 | DOI Listing |
PLoS Pathog
January 2025
Department of Cancer and Genomic Sciences, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom.
Upon infection, human papillomavirus (HPV) manipulates host cell gene expression to create an environment that is supportive of a productive and persistent infection. The virus-induced changes to the host cell's transcriptome are thought to contribute to carcinogenesis. Here, we show by RNA-sequencing that oncogenic HPV18 episome replication in primary human foreskin keratinocytes (HFKs) drives host transcriptional changes that are consistent between multiple HFK donors.
View Article and Find Full Text PDFDosage-sensitive transcription factors (TFs) underlie altered gene regulation in human developmental disorders, and cell-type specific gene regulation is linked to the reorganization of 3D chromatin during cellular differentiation. Here, we show dose-dependent regulation of chromatin organization by the congenital heart disease (CHD)-linked, lineage-restricted TF TBX5 in human cardiomyocyte differentiation. Genome organization, including compartments, topologically associated domains, and chromatin loops, are sensitive to reduced dosage in a human model of CHD, with variations in response across individual cells.
View Article and Find Full Text PDFThe six subunit Origin Recognition Complex (ORC) is a DNA replication initiator that also promotes heterochromatinization in some species. A multi-omics study in a human cell line with mutations in three subunits of ORC, reveals that the subunits bind to DNA independent of each other rather than as part of a common six-subunit ORC. While DNA-bound ORC2 was seen to compact chromatin and attract repressive histone marks, the activation of chromatin and protection from repressive marks was seen at a large number of sites.
View Article and Find Full Text PDFbioRxiv
January 2025
Division of Hematology and Medical Oncology, Department of Medicine and Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Gene expression is coordinated by a multitude of transcription factors (TFs), whose binding to the genome is directed through multiple interconnected epigenetic signals, including chromatin accessibility and histone modifications. These complex networks have been shown to be disrupted during aging, disease, and cancer. However, profiling these networks across diverse cell types and states has been limited due to the technical constraints of existing methods for mapping DNA:Protein interactions in single cells.
View Article and Find Full Text PDFbioRxiv
November 2024
Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD, USA.
While inputs regulating CD4 T helper cell (Th) differentiation are well-defined, the integration of downstream signaling with transcriptional and epigenetic programs that define Th-lineage identity remain unresolved. PI3K signaling is a critical regulator of T cell function; activating mutations affecting PI3Kδ result in an immunodeficiency with multiple T cell defects. Using mice expressing activated-PI3Kδ, we found aberrant expression of proinflammatory Th1-signature genes under Th2-inducing conditions, both and .
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