The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer

Authors: Klenova E.M.¹; Morse H.C.²; Ohlsson R.³; Lobanenkov V.V.²

Source: Seminars in Cancer Biology, Volume 12, Number 5, October 2002 , pp. 399-414(16)

Publisher: Academic Press

Abstract:

CTCF is a ubiquitous 11 zinc finger (ZF) protein with highly versatile functions: in addition to transcriptional silencing or activating in a context-dependent fashion, it organizes epigenetically controlled chromatin insulators that regulate imprinted genes in soma. Recently, we have identified a CTCF paralogue, termed BORISfor Brother of the Regulator of Imprinted Sites, that is expressed only in the testis. BORIS has the same exons encoding the 11 ZF domain as mammalian CTCF genes, and hence interacts with similar ciselements, but encodes amino and carboxy termini distinct from those in CTCF. Normally, CTCF and BORIS are expressed in a mutually exclusive pattern that correlates with re-setting of methylation marks during male germ cell differentiation. The antagonistic features of these two gene siblings are underscored by showing that while CTCF overexpression blocks cell proliferation, expression of BORIS in normally BORIS-negative cells promotes cell growth which can lead to transformation. The suggestion that BORIS directs epigenetic reprogramming at CTCF target sites impinges on the observations that human BORIS is not only abnormally activated in a wide range of human cancers, but also maps to the cancer-associated amplification region at 20q13. The sibling rivalry occasioned by aberrant expression of BORIS in cancer may interfere with normal functions of CTCF including growth suppression, and contribute to epigenetic dysregulation which is a common feature in human cancer.

© 2002 Elsevier Science Ltd

Language: English

Document Type: Research article

Affiliations: 1: Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester CQ4 3SQ, UK 2: Section of Molecular Pathology, Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Twinbrook I bldg, 5640 Fishers Lane, Rockville, MD 20852, USA 3: Department of Genetics and Pathology and Department of Development and Genetics, Uppsala University, Norbyva¨gen 18A, S-752 36 Uppsala, Sweden

Publication date: 2002-10-01

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• In this Subject: Biology ,  Oncology
• By this author: Klenova E.M. ;  Morse H.C. ;  Ohlsson R. ;  Lobanenkov V.V.

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