Publication in detail

Journal Mol Cell Biol 2010 May;30(10):2473-84. Epub 2010 Mar

Expression of a testis-specific form of Gal3st1 (CST), a gene essential for spermatogenesis, is regulated by the CTCF paralogous gene, BORIS

Abdullaev, Z; Kosaka-Suzuki, N; Lobanenkov, V.; Loukinov, D; Morse, HC 3rd; Pack, S; Pugacheva, E; Shin, DM; Suzuki, T; Yoon, J

Laboratory of Immunopathology, National Institutes of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA.

Abstract:
Previously, it was shown that the CTCF paralogous gene, BORIS (brother of the regulator of imprinted sites) is expressed in male germ cells, but its function in spermatogenesis has not been defined. To develop an understanding of the functional activities of BORIS, we generated BORIS knockout (KO) mice. Mice homozygous for the null allele had a defect in spermatogenesis that resulted in small testes associated with increased cell death. The defect was evident as early as postnatal day 21 and was manifested by delayed production of haploid cells. By gene expression profiling, we found that transcript levels for Gal3st1 (also known as cerebroside sulfotransferase [CST]), known to play a crucial role in meiosis, were dramatically reduced in BORIS KO testes. We found that CST is expressed in testis as a novel testis-specific isoform, CST form F(TS), that has a short exon 1f. We showed that BORIS bound to and activated the promoter of CST form F(TS). Mutation of the BORIS binding site in the promoter reduced the ability of BORIS to activate the promoter. These findings define transcriptional regulation of CST expression as a critical role for BORIS in spermatogenesis.

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