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.
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.
Loukinov
Dmitri I
DI
Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0760, USA.
Pugacheva
Elena
E
Vatolin
Sergei
S
Pack
Svetlana D
SD
Moon
Hanlim
H
Chernukhin
Igor
I
Mannan
Poonam
P
Larsson
Erik
E
Kanduri
Chandrasekhar
C
Vostrov
Alexander A
AA
Cui
Hengmi
H
Niemitz
Emily L
EL
Rasko
John E J
JE
Docquier
France M
FM
Kistler
Malathi
M
Breen
Joseph J
JJ
Zhuang
Zhengping
Z
Quitschke
Wolfgang W
WW
Renkawitz
Rainer
R
Klenova
Elena M
EM
Feinberg
Andrew P
AP
Ohlsson
Rolf
R
Morse
Herbert C
HC
Lobanenkov
Victor V
VV
D000595:Amino Acid Sequence; D000818:Animals; D000076246:CCCTC-Binding Factor; D003001:Cloning, Molecular; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D005819:Genetic Markers; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; C456540:CTCFL protein, human; C000619698:Ctcf protein, mouse; C499208:Ctcfl protein, mouse; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D012097:Repressor Proteins; D014157:Transcription Factors