Studies in the Molecular Pathology Section center on the activities of two proteins, CTCF and BORIS, and their roles in normal biology and cancer. CTCF is a ubiquitous, 11-zinc-finger DNA-binding protein involved in transcriptional regulation, reading of imprinted sites, X-chromosome inactivation, and enhancer blocking/insulator function.BORIS is a paralogous gene that carries the same DNA binding domain as CTCF but is normally expressed only in spermatocytes. In cancer, CTCF appears to function as a tumor suppressor gene. BORIS is aberrantly expressed in many cancers and is thus a cancer
In cancer, CTCF appears to function as a tumor suppressor gene. BORIS is aberrantly expressed in many cancers and is thus a cancer/testis gene and a possible target for immunotherapy. Approaches from cell and molecular biology as well as transgenic and knockout mice are used to probe the functions of these uniquely paired proteins.
Dr. Lobanenkov received an M.A. in nuclear physics from the Institute of Physics in 1977 and a Ph.D. in experimental oncology from the Cancer Research Center, Moscow, in 1981. He was molecular carcinogenesis team leader in the All-Union Cancer Center of the former U.S.S.R. and a visiting scholar at the Royal Cancer Hospital, London, until 1990, where he discovered avian CTCF. He was invited to the Fred Hutchinson Cancer Research Center in Seattle as a foreign faculty-in-residence funded by NIH grants.
In 1999, he became chief of the Molecular Pathology Section in the Laboratory of Immunopathology; identified CTCF in Drosophila, mice, and man; and characterized the novel BORIS+CTCF gene family universally involved in epigenetic regulation of mammalian cellular and viral genomes. His section, which moved to the Laboratory of Immunogenetics in 2012, works to understand how genome-wide, CTCF/BORIS-binding sequences regulate different functions, including inter- and intra-chromosomal 3-D DNA-looping interactions, mono-allelic expression of imprinted and non-imprinted genes, X-chromosome inactivation, and regulation of stem/germ cell-specific promoters associated with targeted DNA demethylation.
- Rivero-Hinojosa S, Pugacheva EM, Kang S, Méndez-Catalá CF, Kovalchuk AL, Strunnikov AV, Loukinov D, Lee JT, Lobanenkov VV. The combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis. Nat Commun. 2021;12(1):3846.
- Pugacheva EM, Kubo N, Loukinov D, Tajmul M, Kang S, Kovalchuk AL, Strunnikov AV, Zentner GE, Ren B, Lobanenkov VV. CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention. Proc Natl Acad Sci U S A. 2020;117(4):2020-2031.
- Pugacheva EM, Rivero-Hinojosa S, Espinoza CA, Méndez-Catalá CF, Kang S, Suzuki T, Kosaka-Suzuki N, Robinson S, Nagarajan V, Ye Z, Boukaba A, Rasko JE, Strunnikov AV, Loukinov D, Ren B, Lobanenkov VV. Comparative analyses of CTCF and BORIS occupancies uncover two distinct classes of CTCF binding genomic regions. Genome Biol. 2015;16:161.
- Lobanenkov VV, Zentner GE. Discovering a binary CTCF code with a little help from BORIS. Nucleus. 2018;9(1):33-41.
- Pugacheva EM, Teplyakov E, Wu Q, Li J, Chen C, Meng C, Liu J, Robinson S, Loukinov D, Boukaba A, Hutchins AP, Lobanenkov V, Strunnikov A. The cancer-associated CTCFL/BORIS protein targets multiple classes of genomic repeats, with a distinct binding and functional preference for humanoid-specific SVA transposable elements. Epigenetics Chromatin. 2016;9(1):35.
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Molecular Biology and Biochemistry
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This page was last updated on Thursday, August 11, 2022