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bioRxiv · 10.1101/2021.04.27.441659

The combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis

Rivero Hinojosa, S.·Pugacheva, E. M.·Kang, S.·Mendez Catala, C. F.·Kovalchuk, A. L.·Strunnikov, A. V.·Loukinov, D.·Lee, J. T.·Lobanenkov, V. V.
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Abstract

CTCF is a key organizer of the 3D genome. Its specialized paralog, BORIS, heterodimerizes with CTCF but is expressed only in male germ cells and in cancer states. Unexpectedly, BORIS-null mice have only minimal germ cell defects. To understand the CTCF-BORIS relationship, mouse models with varied CTCF and BORIS levels were generated. Whereas Ctcf+/+Boris+/+, Ctcf+/- Boris+/+, and Ctcf+/+Boris-/- males are fertile, Ctcf+/-Boris-/- (Compound Mutant; CM) males are sterile. Testes with combined depletion of both CTCF and BORIS show reduced size, defective meiotic recombination, increased apoptosis, and malformed spermatozoa. Although CM germ cells exhibit only 25% of CTCF WT expression, chromatin binding of CTCF is preferentially lost from CTCF-BORIS heterodimeric sites. Furthermore, CM testes lose the expression of a large number of spermatogenesis genes and gain the expression of developmentally inappropriate genes that are "toxic" to fertility. Thus, a combined action of CTCF and BORIS is required to both repress pre-meiotic genes and activate post-meiotic genes for a complete spermatogenesis program.

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Rivero Hinojosa, S., Pugacheva, E. M., Kang, S., Mendez Catala, C. F., Kovalchuk, A. L., Strunnikov, A. V., Loukinov, D., Lee, J. T., Lobanenkov, V. V.. 2021-04-28. The combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis. https://doi.org/10.1101/2021.04.27.441659

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