There is still only 1 review devoted in full by Klenova et. al. to the entire CTCF & BORIS family of paralogous 11 ZF TransFactors evolved via duplication of an ancestral CTCF 11 ZFs conserved from Insects to Humans

Published: 29-03-2018| Version 1 | DOI: 10.17632/tdcw7r92zv.1
Contributor:
Victor Lobanenkov

Description

CTCF has been discovered by Victor Lobanenkov in late 80's and subsequently cloned by Elena Klenova, Galina Filippova, Elena Pugacheva, Dmitry Loukinov in collaboration with other members of the so-named Victor's "CTCF & BORIS Discovery Teams" who are respectively responsible for both identification and characterization of the very first full-length CTCF cDNA clones isolated initially from birds (E. Klenova et. al. Mol. Cell. Biol., 1993) and secondly obtained together with mapping & sequencing an entire genomic CTCF loci from mice, rats, and humans (G. Filippova et. al. Mol. Cell. Biol., 1996) which included a stunning observation made with regard to a truly exceptional evolutionary preservation of individual amino acids across the whole CTCF DNA-Binding Domain ("CTCF DBD") comprised of 10 C2H2-class and 1 C2HC-ype Zinc Fingers (a.k.a. the central "11 ZF" CTCF DBD) since it was found to be almost 100% conserved throughout vertebrae evolution from CTCF in a bony fish (cloned from Zebra Fish by E. Pugacheva et. al. Gene, 2005) to CTCF in primates and CTCF in humans. Remarkably, when the same Lobanenkov' team have also cloned CTCF gene and CTCF cDNA from one of the most commonly used species of Insect' Kingdom (submitted by G.F. and V.L. into international "GenBank' repository by the year of 2000) and had published Drosophila CTCF (a.k.a. "dCTCF" by Hanlim Moon et. al. in 2005 EMBO Reports), it become clear that a truly ubiquitous 11 ZF CTCF proteins possess highly versatile functions in all multi-cellular organisms from Drososophila to humans. 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 BORIS for 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 cis elements, 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.

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