RESUMEN
BACKGROUND: The CCCTC-binding factor (CTCF) is a highly conserved insulator protein that plays various roles in many cellular processes. CTCF is one of the main architecture proteins in higher eukaryotes, and in combination with other architecture proteins and regulators, also shapes the three-dimensional organization of a genome. Experiments show CTCF partially remains associated with chromatin during mitosis. However, the role of CTCF in the maintenance and propagation of genome architectures throughout the cell cycle remains elusive. RESULTS: We performed a comprehensive bioinformatics analysis on public datasets of Drosophila CTCF (dCTCF). We characterized dCTCF-binding sites according to their occupancy status during the cell cycle, and identified three classes: interphase-mitosis-common (IM), interphase-only (IO) and mitosis-only (MO) sites. Integrated function analysis showed dCTCF-binding sites of different classes might be involved in different biological processes, and IM sites were more conserved and more intensely bound. dCTCF-binding sites of the same class preferentially localized closer to each other, and were highly enriched at chromatin syntenic and topologically associating domains boundaries. CONCLUSIONS: Our results revealed different functions of dCTCF during the cell cycle and suggested that dCTCF might contribute to the establishment of the three-dimensional architecture of the Drosophila genome by maintaining local chromatin compartments throughout the whole cell cycle.
Asunto(s)
Animales , Proteínas Represoras/fisiología , Cromatina/fisiología , Proteínas de Drosophila/fisiología , Drosophila melanogaster/química , Genoma de los Insectos/genética , Mitosis/fisiología , Sitios de Unión , Secuencia de Bases , Ciclo Celular/fisiología , Secuencia Conservada , Biología Computacional , Sintenía , Ensamble y Desensamble de Cromatina/fisiología , Anotación de Secuencia Molecular , Conjuntos de Datos como Asunto , Factor de Unión a CCCTC , Interfase/fisiologíaRESUMEN
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.
Asunto(s)
Humanos , Factor de Unión a CCCTC , Enfermedad , Genética , Epigenómica , Métodos , Proteínas Represoras , Genética , Factores de Transcripción , Genética , Dedos de Zinc , GenéticaRESUMEN
To investigate the function of CTCF and understand the pathogenesis of tumors better, we produced rabbit polyclonal antibody of human transcription factor CTCF protein and detected its expression in several kinds of human cancer cells and tissues. GST fusion protein of human CTCF-N domain was purified by GSTrap-FF affinity chromatography and was successfully expressed under induction of IPTG in E. coli BL21. Western blotting analysis demonstrated that the polyclonal antibody can recognize the endogenous CTCF from HepG2, MCF-7 and HeLa cells specifically. The produced antibodies can be used for gene expression regulation and tissue distribution study at protein level.