Description of Research Program

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/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.

Selected Recent Publications

(View list in PubMed.)

CF Qi, Martensson A, Mattioli M, Dalla-Favera R, Lobanenkov VV, Morse HC 3rd. CTCF functions as a critical regulator of cell-cycle arrest and death afterligation of the B cell receptor on immature B cells. Proc Natl Acad Sci USA. 2003. 100(2): 633-638. 

Klenova EM, Morse HC 3rd, Ohlsson R, Lobanenkov VV. The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer. Semin Cancer Biol. 2002. 12(5):399-414. Review.

DI Loukinov, Pugacheva E, Vatolin S, Pack SD, Moon H, Chernukhin I, Mannan P, Larsson E, Kanduri C, Vostrov AA, Cui H, Niemitz EL, Rasko JE, Docquier FM, Kistler M, Breen JJ, Zhuang Z, Quitschke WW, Renkawitz R, Klenova EM, Feinberg AP, Ohlsson R, Morse HC 3rd, Lobanenkov VV. BORIS, a novel male germ-line-specific protein associated with epigenetic reprogramming events, shares the same 11-zinc-finger domain with CTCF, the insulator protein involved in reading imprinting marks in the soma. Proc Natl Acad Sci USA. 2002. 99(10): 6806-6811.

Filippova GN, Qi CF, Ulmer JE, Moore JM, Ward MD, Hu YJ, Loukinov DI, Pugacheva EM, Klenova EM, Grundy PE, Feinberg AP, Cleton-Jansen AM, Moerland EW, Cornelisse CJ, Suzuki H, Komiya A, Lindblom A, Dorion-Bonnet F, Neiman PE, Morse HE 3rd, Collins SJ, Lobanenkov VV. Tumor-associated zinc finger mutations in the CTCF transcription factor selectively alter tts DNA-binding specificity. Cancer Res. 2002. 62(1): 48-52.

Rasko JE, Klenova EM, Leon J, Filippova GN, Loukinov DI, Vatolin S,  Robinson AF, Hu YJ, Ulmer J, Ward MD, Pugacheva EM, Neiman PE, Morse HE 3rd, Collins SJ, Lobanenkov VV. Cell growth inhibition by the multifunctional multivalent zinc-finger factor CTCF. Cancer Res. 2001. 61(16): 6002-6007.

Filippova GN, Thienes CP, Penn BH, Cho DH, Hu YJ, Moore JM, Klesert TR, Lobanenkov VV, Tapscott SJ. CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus. Nat Genet. 2001. 28(4): 335-343.

View publications before 2000

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