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The combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis
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 CT...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219828/ https://www.ncbi.nlm.nih.gov/pubmed/34158481 http://dx.doi.org/10.1038/s41467-021-24140-6 |
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author | Rivero-Hinojosa, Samuel Pugacheva, Elena M. Kang, Sungyun Méndez-Catalá, Claudia Fabiola Kovalchuk, Alexander L. Strunnikov, Alexander V. Loukinov, Dmitri Lee, Jeannie T. Lobanenkov, Victor V. |
author_facet | Rivero-Hinojosa, Samuel Pugacheva, Elena M. Kang, Sungyun Méndez-Catalá, Claudia Fabiola Kovalchuk, Alexander L. Strunnikov, Alexander V. Loukinov, Dmitri Lee, Jeannie T. Lobanenkov, Victor V. |
author_sort | Rivero-Hinojosa, Samuel |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8219828 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-82198282021-07-09 The combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis Rivero-Hinojosa, Samuel Pugacheva, Elena M. Kang, Sungyun Méndez-Catalá, Claudia Fabiola Kovalchuk, Alexander L. Strunnikov, Alexander V. Loukinov, Dmitri Lee, Jeannie T. Lobanenkov, Victor V. Nat Commun Article 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. Nature Publishing Group UK 2021-06-22 /pmc/articles/PMC8219828/ /pubmed/34158481 http://dx.doi.org/10.1038/s41467-021-24140-6 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Rivero-Hinojosa, Samuel Pugacheva, Elena M. Kang, Sungyun Méndez-Catalá, Claudia Fabiola Kovalchuk, Alexander L. Strunnikov, Alexander V. Loukinov, Dmitri Lee, Jeannie T. Lobanenkov, Victor V. The combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis |
title | The combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis |
title_full | The combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis |
title_fullStr | The combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis |
title_full_unstemmed | The combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis |
title_short | The combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis |
title_sort | combined action of ctcf and its testis-specific paralog boris is essential for spermatogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219828/ https://www.ncbi.nlm.nih.gov/pubmed/34158481 http://dx.doi.org/10.1038/s41467-021-24140-6 |
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