• PMID: 28475176
• Gene Name: TBL1XR1
• Condition: Play a role in sperm differentiation
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Play a role in sperm differentiation

SLY regulates genes involved in chromatin remodeling and interacts with TBL1XR1 during sperm differentiation

Moretti C, Serrentino ME, Ialy-Radio C, Delessard M, Soboleva TA, Tores F, Leduc M, Nitschké P, Drevet JR, Tremethick DJ, Vaiman D, Kocer A, Cocquet J.

Sperm differentiation requires unique transcriptional regulation and chromatin remodeling after meiosis to ensure proper compaction and protection of the paternal genome. Abnormal sperm chromatin remodeling can induce sperm DNA damage, embryo lethality and male infertility, yet, little is known about the factors which regulate this process. Deficiency in Sly, a mouse Y chromosome-encoded gene expressed only in postmeiotic male germ cells, has been shown to result in the deregulation of hundreds of sex chromosome-encoded genes associated with multiple sperm differentiation defects and subsequent male infertility. The underlying mechanism remained, to date, unknown. Here, we show that SLY binds to the promoter of sex chromosome-encoded and autosomal genes highly expressed postmeiotically and involved in chromatin regulation. Specifically, we demonstrate that Sly knockdown directly induces the deregulation of sex chromosome-encoded H2A variants and of the H3K79 methyltransferase DOT1L. The modifications prompted by loss of Sly alter the postmeiotic chromatin structure and ultimately result in abnormal sperm chromatin remodeling with negative consequences on the sperm genome integrity. Altogether our results show that SLY is a regulator of sperm chromatin remodeling. Finally we identified that SMRT/N-CoR repressor complex is involved in gene regulation during sperm differentiation since members of this complex, in particular TBL1XR1, interact with SLY in postmeiotic male germ cells. FAU - Moretti, Charlotte AU - Moretti C AD - Department of Development, Reproduction and Cancer, INSERM, U1016, Institut Cochin, Paris, France. AD - CNRS, UMR8104, Paris, France. AD - Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France. FAU - Serrentino, Maria-Elisabetta AU - Serrentino ME AD - Department of Development, Reproduction and Cancer, INSERM, U1016, Institut Cochin, Paris, France. AD - CNRS, UMR8104, Paris, France. AD - Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France. FAU - Ialy-Radio, Côme AU - Ialy-Radio C AD - Department of Development, Reproduction and Cancer, INSERM, U1016, Institut Cochin, Paris, France. AD - CNRS, UMR8104, Paris, France. AD - Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France. FAU - Delessard, Marion AU - Delessard M AD - Department of Development, Reproduction and Cancer, INSERM, U1016, Institut Cochin, Paris, France. AD - CNRS, UMR8104, Paris, France. AD - Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France. FAU - Soboleva, Tatiana A AU - Soboleva TA AD - The John Curtin School of Medical Research, The Australian National University, PO Box 334, Canberra, ACT 2601, Australia. FAU - Tores, Frederic AU - Tores F AD - Bioinformatics facility, Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine, Paris, France. FAU - Leduc, Marjorie AU - Leduc M AD - 3P5 proteomic facility, Institut Cochin, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. FAU - Nitschké, Patrick AU - Nitschké P AD - Bioinformatics facility, Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine, Paris, France. FAU - Drevet, Joel R AU - Drevet JR AD - Genetic Reproduction and Development, CNRS UMR6293 - INSERM U1103 - Clermont Université, 63178 Aubière Cedex, France. FAU - Tremethick, David J AU - Tremethick DJ AD - The John Curtin School of Medical Research, The Australian National University, PO Box 334, Canberra, ACT 2601, Australia. FAU - Vaiman, Daniel AU - Vaiman D AUID- ORCID: 0000-0002-1915-0717 AD - Department of Development, Reproduction and Cancer, INSERM, U1016, Institut Cochin, Paris, France. AD - CNRS, UMR8104, Paris, France. AD - Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France. FAU - Kocer, Ayhan AU - Kocer A AD - Genetic Reproduction and Development, CNRS UMR6293 - INSERM U1103 - Clermont Université, 63178 Aubière Cedex, France.