Molecular architecture of CTCFL

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 06/2010; 396(3):648-50. DOI: 10.1016/j.bbrc.2010.04.146
Source: PubMed


The CTCF-like protein, CTCFL, is a DNA-binding factor that regulates the transcriptional program of mammalian male germ cells. CTCFL consists of eleven zinc fingers flanked by polypeptides of unknown structure and function. We determined that the C-terminal fragment predominantly consists of extended and unordered content. Computational analysis predicts that the N-terminal segment is also disordered. The molecular architecture of CTCFL may then be similar to that of its paralog, the CCCTC-binding factor, CTCF. We speculate that sequence divergence in the unstructured terminal segments results in differential recruitment of cofactors, perhaps defining the functional distinction between CTCF in somatic cells and CTCFL in the male germ line.

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    • "The CCCTC-binding factor (CTCF) and its paralog Brother of the Regulator of Imprinted Sites (BORIS) are implicated in epigenetic reprogramming events. Typically, CTCF and BORIS are expressed in a mutually exclusive pattern that correlates with the resetting of methylation marks during male germ cell differentiation (Loukinov et al., 2002; Pugacheva et al., 2010; Campbell et al., 2010). BORIS is considered to be a new oncogene, as abnormally high levels of BORIS transcripts have been observed in a wide range of human tumors and cancer-derived cell lines, and its expression coincides with CpG hypomethylation in cancer cells (Klenova et al., 2002; Woloszynska-Read et al., 2011; Kleiner, 2012). "
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    ABSTRACT: We investigated the expression of Brother of Regulator of Imprinted Sites (BORIS) and CCCTC-binding factor (CTCF) in squamous intraepithelial lesions and cervical cancer. To analyze BORIS and CTCF expression, an endocervical cytobrush sample was taken for total RNA isolation. CTCF and BORIS mRNA was quantified from total RNA using quantitative reverse transcription-polymerase chain reaction. A total of 71 samples were collected and classified according to the Bethesda Classification of squamous intraepithelial lesions. BORIS expression was observed in 9 (12.7%) samples; of these, 5.3, 5.9, 14.8, and 37.5% in the groups that were cytology negative for intraepithelial lesion or malignancy, low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), and invasive cervical carcinoma, respectively. The expression level of BORIS was significantly higher in the group with invasive cervical carcinoma as compared with the groups negative for intraepithelial lesion or malignancy, LSIL, and HSIL (P < 0.0005). CTCF mRNA was expressed in all samples. CTCF expression was significantly higher in carcinoma groups compared with LSIL, HSIL, and negative for intraepithelial lesion or malignancy groups. We found that BORIS and CTCF expressions in the LSIL and invasive cervical carcinoma groups were higher than expression in cytological normal samples. Additional studies should be conducted to examine the function of transcription factors during different stages of the transformation of cervical cancer cells.
    Full-text · Article · Jul 2015 · Genetics and molecular research: GMR
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    • "CTCF and BORIS might thus bind to the same DNA target sequences. On the contrary, the flanking N- and C- terminal regions show very little sequence homology between of BORIS and CTCF, implying that they may recruit different associated cofactors [11], [12], [13]. "
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    ABSTRACT: CTCF is a ubiquitous epigenetic regulator that has been proposed as a master keeper of chromatin organisation. CTCF-like, or BORIS, is thought to antagonise CTCF and has been found in normal testis, ovary and a large variety of tumour cells. The cellular function of BORIS remains intriguing although it might be involved in developmental reprogramming of gene expression patterns. We here unravel the expression of CTCF and BORIS proteins throughout human epidermis. While CTCF is widely distributed within the nucleus, BORIS is confined to the nucleolus and other euchromatin domains. Nascent RNA experiments in primary keratinocytes revealed that endogenous BORIS is present in active transcription sites. Interestingly, BORIS also localises to interphase centrosomes suggesting a role in the cell cycle. Blocking the cell cycle at S phase or mitosis, or causing DNA damage, produced a striking accumulation of BORIS. Consistently, ectopic expression of wild type or GFP- BORIS provoked a higher rate of S phase cells as well as genomic instability by mitosis failure. Furthermore, down-regulation of endogenous BORIS by specific shRNAs inhibited both RNA transcription and cell cycle progression. The results altogether suggest a role for BORIS in coordinating S phase events with mitosis.
    Full-text · Article · Jun 2012 · PLoS ONE
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    • "Therefore, it may actually be the protein partners of CTCF and BORIS that ultimately determine their specific cellular function at a specific location. The importance of these interactions seems to be supported by the fact that an analysis of the amino and carboxyl protein domains of BORIS shows them to be largely unstructured molecules suggesting that their architecture may be organized through their protein associations [24]. "
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    ABSTRACT: BORIS, or CTCFL, the so called Brother of the Regulator of Imprinted Sites because of the extensive homology in the central DNA binding region of the protein to the related regulator, CTCF, is expressed in early gametogenesis and in multiple cancers but not in differentiated somatic cells. Thus it is a member of the cancer testes antigen group (CTAs). Since BORIS and CTCF target common DNA binding sites, these proteins function on two levels, the first level is their regulation via the methylation context of the DNA target site and the second level is their distinct and different epigenetic associations due to differences in the non-homologous termini of the proteins. The regulation on both of these levels is extensive and complex and the sphere of influence of each of these proteins is associated with vastly different cellular signaling processes. On the level of gene expression, BORIS has three known promoters and multiple spliced mRNAs which adds another level of complexity to this intriguing regulator. BORIS expression is observed in the majority of cancer tissues and cell lines analyzed up to today. The expression profile and essential role of BORIS in cancer make this molecule very attractive target for cancer immunotherapy. This review summarizes what is known about BORIS regarding its expression, structure, and function and then presents some theoretical considerations with respect to its genome wide influence and its potential for use as a vaccine for cancer immunotherapy.
    Full-text · Article · Dec 2011 · Journal of Translational Medicine
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