SLY Regulates Genes Involved in Chromatin Remodeling and Interacts with TBL1XR1 During Sperm Differentiation

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2017 May 6

PMID 28475176

Citations 20

Authors

Charlotte Moretti

Maria-Elisabetta Serrentino

Come Ialy-Radio

Marion Delessard

Tatiana A Soboleva

Frederic Tores

Marjorie Leduc

Patrick Nitschke

Joel R Drevet

David J Tremethick

Daniel Vaiman

Ayhan Kocer

Julie Cocquet

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Fluo-Cast-Bright: a deep learning pipeline for the non-invasive prediction of chromatin structure and developmental potential in live oocytes.

Zhang X, Baumann C, De La Fuente R Commun Biol. 2025; 8(1):141.

PMID: 39880880 PMC: 11779945. DOI: 10.1038/s42003-025-07568-0.

Chromatin environment-dependent effects of DOT1L on gene expression in male germ cells.

Coulee M, de la Iglesia A, Blanco M, Gobe C, Lapoujade C, Ialy-Radio C Commun Biol. 2025; 8(1):138.

PMID: 39875559 PMC: 11775102. DOI: 10.1038/s42003-024-07393-x.

Genetic conflict and the origin of multigene families: implications for sex chromosome evolution.

Marti E, Larracuente A Proc Biol Sci. 2023; 290(2010):20231823.

PMID: 37909083 PMC: 10618873. DOI: 10.1098/rspb.2023.1823.

Casting histone variants during mammalian reproduction.

Karam G, Molaro A Chromosoma. 2023; 132(3):153-165.

PMID: 37347315 PMC: 10356639. DOI: 10.1007/s00412-023-00803-9.

Generation and Characterization of a Transgenic Mouse That Specifically Expresses the Cre Recombinase in Spermatids.

Gobe C, Ialy-Radio C, Pierre R, Cocquet J Genes (Basel). 2023; 14(5).

PMID: 37239343 PMC: 10217838. DOI: 10.3390/genes14050983.

References

Helleu Q, Gerard P, Montchamp-Moreau C . Sex chromosome drive. Cold Spring Harb Perspect Biol. 2014; 7(2):a017616. PMC: 4315933. DOI: 10.1101/cshperspect.a017616. View

Spiess A, Feig C, Schulze W, Chalmel F, Cappallo-Obermann H, Primig M . Cross-platform gene expression signature of human spermatogenic failure reveals inflammatory-like response. Hum Reprod. 2007; 22(11):2936-46. DOI: 10.1093/humrep/dem292. View

Subramanian A, Tamayo P, Mootha V, Mukherjee S, Ebert B, Gillette M . Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102(43):15545-50. PMC: 1239896. DOI: 10.1073/pnas.0506580102. View

Tan M, Luo H, Lee S, Jin F, Yang J, Montellier E . Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell. 2011; 146(6):1016-28. PMC: 3176443. DOI: 10.1016/j.cell.2011.08.008. View

Feng Q, Wang H, Ng H, Erdjument-Bromage H, Tempst P, Struhl K . Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain. Curr Biol. 2002; 12(12):1052-8. DOI: 10.1016/s0960-9822(02)00901-6. View

Li W, Wu J, Kim S, Zhao M, Hearn S, Zhang M . Chd5 orchestrates chromatin remodelling during sperm development. Nat Commun. 2014; 5:3812. PMC: 4151132. DOI: 10.1038/ncomms4812. View

Perissi V, Jepsen K, Glass C, Rosenfeld M . Deconstructing repression: evolving models of co-repressor action. Nat Rev Genet. 2010; 11(2):109-23. DOI: 10.1038/nrg2736. View

Shima J, McLean D, McCarrey J, Griswold M . The murine testicular transcriptome: characterizing gene expression in the testis during the progression of spermatogenesis. Biol Reprod. 2004; 71(1):319-30. DOI: 10.1095/biolreprod.103.026880. View

Moretti C, Vaiman D, Tores F, Cocquet J . Expression and epigenomic landscape of the sex chromosomes in mouse post-meiotic male germ cells. Epigenetics Chromatin. 2016; 9:47. PMC: 5081929. DOI: 10.1186/s13072-016-0099-8. View

10.

Comptour A, Moretti C, Serrentino M, Auer J, Ialy-Radio C, Ward M . SSTY proteins co-localize with the post-meiotic sex chromatin and interact with regulators of its expression. FEBS J. 2014; 281(6):1571-84. PMC: 3960347. DOI: 10.1111/febs.12724. View

11.

Syrjanen J, Pellegrini L, Davies O . A molecular model for the role of SYCP3 in meiotic chromosome organisation. Elife. 2014; 3. PMC: 4102245. DOI: 10.7554/eLife.02963. View

12.

Ramirez F, Dundar F, Diehl S, Gruning B, Manke T . deepTools: a flexible platform for exploring deep-sequencing data. Nucleic Acids Res. 2014; 42(Web Server issue):W187-91. PMC: 4086134. DOI: 10.1093/nar/gku365. View

13.

Bastos H, Lassalle B, Chicheportiche A, Riou L, Testart J, Allemand I . Flow cytometric characterization of viable meiotic and postmeiotic cells by Hoechst 33342 in mouse spermatogenesis. Cytometry A. 2005; 65(1):40-9. DOI: 10.1002/cyto.a.20129. View

14.

Soh Y, Alfoldi J, Pyntikova T, Brown L, Graves T, Minx P . Sequencing the mouse Y chromosome reveals convergent gene acquisition and amplification on both sex chromosomes. Cell. 2014; 159(4):800-13. PMC: 4260969. DOI: 10.1016/j.cell.2014.09.052. View

15.

Zhang W, Hayashizaki Y, Kone B . Structure and regulation of the mDot1 gene, a mouse histone H3 methyltransferase. Biochem J. 2003; 377(Pt 3):641-51. PMC: 1223909. DOI: 10.1042/BJ20030839. View

16.

Yoon H, Chan D, Reynolds A, Qin J, Wong J . N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso. Mol Cell. 2003; 12(3):723-34. DOI: 10.1016/j.molcel.2003.08.008. View

17.

Zhang D, Yoon H, Wong J . JMJD2A is a novel N-CoR-interacting protein and is involved in repression of the human transcription factor achaete scute-like homologue 2 (ASCL2/Hash2). Mol Cell Biol. 2005; 25(15):6404-14. PMC: 1190321. DOI: 10.1128/MCB.25.15.6404-6414.2005. View

18.

Wong M, Medrano J . Real-time PCR for mRNA quantitation. Biotechniques. 2005; 39(1):75-85. DOI: 10.2144/05391RV01. View

19.

Reynard L, Cocquet J, Burgoyne P . The multi-copy mouse gene Sycp3-like Y-linked (Sly) encodes an abundant spermatid protein that interacts with a histone acetyltransferase and an acrosomal protein. Biol Reprod. 2009; 81(2):250-7. PMC: 2849823. DOI: 10.1095/biolreprod.108.075382. View

20.

Gaucher J, Boussouar F, Montellier E, Curtet S, Buchou T, Bertrand S . Bromodomain-dependent stage-specific male genome programming by Brdt. EMBO J. 2012; 31(19):3809-20. PMC: 3463845. DOI: 10.1038/emboj.2012.233. View