Characterization of constitutive CTCF/cohesin loci: a possible role in establishing topological domains in mammalian genomes

BMC Genomics (Impact Factor: 4.04). 08/2013; 14(1):553. DOI: 10.1186/1471-2164-14-553
Source: PubMed

ABSTRACT Recent studies suggested that human/mammalian genomes are divided into large, discrete domains that are units of chromosome organization. CTCF, a CCCTC binding factor, has a diverse role in genome regulation including transcriptional regulation, chromosome-boundary insulation, DNA replication, and chromatin packaging. It remains unclear whether a subset of CTCF binding sites plays a functional role in establishing/maintaining chromatin topological domains.
We systematically analysed the genomic, transcriptomic and epigenetic profiles of the CTCF binding sites in 56 human cell lines from ENCODE. We identified ~24,000 CTCF sites (referred to as constitutive sites) that were bound in more than 90% of the cell lines. Our analysis revealed: 1) constitutive CTCF loci were located in constitutive open chromatin and often co-localized with constitutive cohesin loci; 2) most constitutive CTCF loci were distant from transcription start sites and lacked CpG islands but were enriched with the full-spectrum CTCF motifs: a recently reported 33/34-mer and two other potentially novel (22/26-mer); 3) more importantly, most constitutive CTCF loci were present in CTCF-mediated chromatin interactions detected by ChIA-PET and these pair-wise interactions occurred predominantly within, but not between, topological domains identified by Hi-C.
Our results suggest that the constitutive CTCF sites may play a role in organizing/maintaining the recently identified topological domains that are common across most human cells.


Available from: Weichun Huang, Aug 01, 2014
1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: The study of the three-dimensional organization of chromatin has recently gained much focus in the context of novel techniques for detecting genome-wide contacts using next-generation sequencing. These chromosome conformation capture-based methods give a deep topological insight into the architecture of the genome inside the nucleus. Several recent studies observe a compartmentalization of chromatin interactions into spatially confined domains. This structural feature of interphase chromosomes is not only supported by conventional studies assessing the interaction data of millions of cells, but also by analysis on the level of a single cell. We first present and examine the different models that have been proposed to elucidate these topological domains in eukaryotes. Then we show that a model which relies on the dynamic formation of loops within domains can account for the experimentally observed contact maps. Interestingly, the topological domain structure is not only found in mammalian genomes, but also in bacterial chromosomes. Copyright © 2015. Published by Elsevier B.V.
    FEBS letters 04/2015; DOI:10.1016/j.febslet.2015.04.021 · 3.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: CCCTC-binding factor (CTCF) is the major protein involved in insulator activity in vertebrates, with widespread DNA binding sites in the genome. CTCF participates in many processes related to global chromatin organization and remodeling, contributing to the repression or activation of gene transcription. It is also involved in epigenetic reprogramming and is essential during gametogenesis and embryo development. Abnormal DNA methylation patterns at CTCF motifs may impair CTCF binding to DNA and are related to fertility disorders in mammals. Therefore, CTCF and its binding sites are important candidate regions to be investigated as molecular markers for gamete and embryo quality. This article reviews the role of CTCF in genomic imprinting, gametogenesis and early embryo development and moreover, highlights potential opportunities for environmental influences associated with assisted reproductive techniques (ARTs) to affect CTCF mediated processes. We discuss the potential use of CTCF as a molecular marker for assessing gamete and embryo quality in the context of improving the efficiency and safety of ARTs.
    Biology of Reproduction 10/2014; DOI:10.1095/biolreprod.114.122945 · 3.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: CTCF is a candidate tumor suppressor gene encoding a multifunctional transcription factor. CTCF function is controlled by posttranslational modification and interaction with other proteins. Research findings suggested that CTCF function can be regulated by poly(ADP-ribosyl)ation (PARlation) and has specific anti-apoptotic function in breast cancer cells. The aim of this study is to assess the effect of CTCF-wild type (WT) and CTCF complete mutant, which is deficient of PARlation in regulating apoptosis in breast cancer cells. The effect of CTCF-WT and CTCF complete mutant was expressed in breast cancer cell-lines by DNA-mediated transfection technique monitored by enhanced green fluorescent protein fluorescence. Evaluation of apoptotic cell death was carried out with immunohistochemical staining using 4'-6'-diamino-2 phenylindole and scoring by fluorescent microscopy. CTCF-WT supports survival of breast cancer cells and was observed that CTCF complete mutant interferes with the functions of the CTCF-WT and there was a considerable apoptotic cell death in the breast cancer cell lines such as MDA-MB-435, CAMA-1 and MCF-7. The study enlighten CTCF as a Biological Marker for breast cancer and the role of CTCF PARlation may be involved in breast carcinogenesis.
    Indian journal of medical and paediatric oncology 01/2015; 36(1):49-54. DOI:10.4103/0971-5851.151784