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

doi:10.1073/pnas.092123699

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

^aLaboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0760; ^bSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892; ^cDepartment of Biological Sciences, University of Essex, Wivenhoe Park, Colchester CQ4 3SQ, United Kingdom; Departments of ^dGenetics and Pathology and ^eDevelopment and Genetics, Uppsala University, Norbyvägen 18A, S-752 36 Uppsala, Sweden; ^fDepartment of Psychiatry and Behavioral Science, State University of New York, Stony Brook, NY 11794-8101; ^gInstitute of Genetic Medicine, Johns Hopkins University School of Medicine, Ross 1064, 720 Rutland Avenue, Baltimore, MD 21205; ^hGene Therapy Research Unit, Centenary Institute and Sydney Cancer Centre, Newtown NSW 2042, Australia; ⁱDepartment of Chemistry and Biochemistry and the School of Medicine, University of South Carolina, Columbia, SC 29208; and ^kGenetisches Institut der Justus-Liebig-Universität, Heinrich-Buff-Ring 58-62, 35392 Giessen, Germany

Communicated by George Klein, Karolinska Institute, Stockholm, Sweden (received for review February 6, 2002)

Abstract

CTCF, a conserved, ubiquitous, and highly versatile 11-zinc-finger factor involved in various aspects of gene regulation, forms methylation-sensitive insulators that regulate X chromosome inactivation and expression of imprinted genes. We document here the existence of a paralogous gene with the same exons encoding the 11-zinc-finger domain as mammalian CTCF genes and thus the same DNA-binding potential, but with distinct amino and carboxy termini. We named this gene BORIS for Brother of the Regulator of Imprinted Sites. BORIS is present only in the testis, and expressed in a mutually exclusive manner with CTCF during male germ cell development. We show here that erasure of methylation marks during male germ-line development is associated with dramatic up-regulation of BORIS and down-regulation of CTCF expression. Because BORIS bears the same DNA-binding domain that CTCF employs for recognition of methylation marks in soma, BORIS is a candidate protein for the elusive epigenetic reprogramming factor acting in the male germ line.

Footnotes

↵ j Present address: Transgenomic Inc., 11 Firstfield Road, Suite E, Gaithersburg, MD 20878.
↵ l To whom reprint requests should be addressed at: Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 7, Room 303, 7 Center Drive, MSC 0760, Bethesda, MD 20892. E-mail: vlobanenkov{at}niaid.nih.gov.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession no. AF336042).
↵ m Ohta, T., Khadake, J. R., Rodriguez-Jato, S., Mione, C., Knepper, J. L., Svoboda, P., McCarrey, J. R., Schultz, R. M., Yang, T. P. & Nicholls, R. D. (2001) Am. J. Hum. Genet. 69, 52 (abstr.).
Abbreviations:

ZF,

zinc finger;

ICR,

imprinting control region;

EMSA,

electrophoretic mobility shift assay;

Ab,

antibodies;

RT,

reverse transcription;

NE,

nuclear extracts