Previously Uncharacterized Histone Acetyltransferases Implicated in Mammalian Spermatogenesis

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2002 Jun 20

PMID 12072557

Citations 78

Authors

Bruce T Lahn

Zhao Lan Tang

Jianxin Zhou

Robert J Barndt

Martti Parvinen

C David Allis

David C Page

Affiliations

Soon will be listed here.

Abstract

During spermiogenesis (the maturation of spermatids into spermatozoa) in many vertebrate species, protamines replace histones to become the primary DNA-packaging protein. It has long been thought that this process is facilitated by the hyperacetylation of histone H4. However, the responsible histone acetyltransferase enzymes are yet to be identified. CDY is a human Y-chromosomal gene family expressed exclusively in the testis and implicated in male infertility. Its mouse homolog Cdyl, which is autosomal, is expressed abundantly in the testis. Proteins encoded by CDY and its homologs bear the "chromodomain," a motif implicated in chromatin binding. Here, we show that (i) human CDY and mouse CDYL proteins exhibit histone acetyltransferase activity in vitro, with a strong preference for histone H4; (ii) expression of human CDY and mouse Cdyl genes during spermatogenesis correlates with the occurrence of H4 hyperacetylation; and (iii) CDY and CDYL proteins are localized to the nuclei of maturing spermatids where H4 hyperacetylation takes place. Taken together, these data link human CDY and mouse CDYL to the histone-to-protamine transition in mammalian spermiogenesis. This link offers a plausible mechanism to account for spermatogenic failure in patients bearing deletions of the CDY genes.

Citing Articles

FertilitY Predictor-a machine learning-based web tool for the prediction of assisted reproduction outcomes in men with Y chromosome microdeletions.

Colaco S, Narad P, Singh A, Gupta P, Choudhury A, Sengupta A J Assist Reprod Genet. 2024; 42(2):473-481.

PMID: 39652237 PMC: 11871245. DOI: 10.1007/s10815-024-03338-9.

Chromodomain Y-like (CDYL) inhibition ameliorates acute kidney injury in mice by regulating tubular pyroptosis.

Xiang T, Li L, Li J, Chen X, Guo F, Liu J Acta Pharmacol Sin. 2024; 45(12):2598-2610.

PMID: 39043969 PMC: 11579507. DOI: 10.1038/s41401-024-01345-1.

CDYL loss promotes cervical cancer aggression by increasing PD-L1 expression via the suppression of IRF2BP2 transcription.

Cui Y, Zhao Y, Shen G, Lv Q, Ma L Transl Oncol. 2024; 47:102038.

PMID: 38991463 PMC: 11296252. DOI: 10.1016/j.tranon.2024.102038.

Interaction between Chromodomain Y-like Protein and Androgen Receptor Signaling in Sertoli Cells Accounts for Spermatogenesis.

Lan K, Cheng Y, Chang Y, Wei K, Weng P, Kang H Cells. 2024; 13(10.

PMID: 38786072 PMC: 11120535. DOI: 10.3390/cells13100851.

Cytogenetics investigation in 151 Brazilian infertile male patients and genomic analysis in selected cases: experience of 14 years in a public genetic service.

Adriano M, Bortolai A, Madia F, da Silva Carvalho G, Nascimento A, Zanardo E BMC Res Notes. 2024; 17(1):67.

PMID: 38444014 PMC: 10916190. DOI: 10.1186/s13104-024-06710-1.

References

Lin R, Leone J, Cook R, Allis C . Antibodies specific to acetylated histones document the existence of deposition- and transcription-related histone acetylation in Tetrahymena. J Cell Biol. 1989; 108(5):1577-88. PMC: 2115542. DOI: 10.1083/jcb.108.5.1577. View

Balhorn R . A model for the structure of chromatin in mammalian sperm. J Cell Biol. 1982; 93(2):298-305. PMC: 2112839. DOI: 10.1083/jcb.93.2.298. View

Martinage A, CHEVAILLIER P, Sautiere P . Nuclear basic proteins in spermiogenesis. Biochimie. 1998; 80(2):117-28. DOI: 10.1016/s0300-9084(98)80018-7. View

Oliva R, Mezquita C . Histone H4 hyperacetylation and rapid turnover of its acetyl groups in transcriptionally inactive rooster testis spermatids. Nucleic Acids Res. 1982; 10(24):8049-59. PMC: 327069. DOI: 10.1093/nar/10.24.8049. View

Cavalli G, Paro R . Chromo-domain proteins: linking chromatin structure to epigenetic regulation. Curr Opin Cell Biol. 1998; 10(3):354-60. DOI: 10.1016/s0955-0674(98)80011-2. View

Candau R, Zhou J, Allis C, Berger S . Histone acetyltransferase activity and interaction with ADA2 are critical for GCN5 function in vivo. EMBO J. 1997; 16(3):555-65. PMC: 1169659. DOI: 10.1093/emboj/16.3.555. View

Menke D, Mutter G, Page D . Expression of DAZ, an azoospermia factor candidate, in human spermatogonia. Am J Hum Genet. 1997; 60(1):237-41. PMC: 1712565. View

Palosaari P, Vihinen M, Mantsala P, Alexson S, Pihlajaniemi T, Hiltunen J . Amino acid sequence similarities of the mitochondrial short chain delta 3, delta 2-enoyl-CoA isomerase and peroxisomal multifunctional delta 3, delta 2-enoyl-CoA isomerase, 2-enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase enzyme in rat liver..... J Biol Chem. 1991; 266(17):10750-3. View

Hecht N, Bower P, Waters S, Yelick P, Distel R . Evidence for haploid expression of mouse testicular genes. Exp Cell Res. 1986; 164(1):183-90. DOI: 10.1016/0014-4827(86)90465-9. View

10.

Parvinen M, Hecht N . Identification of living spermatogenic cells of the mouse by transillumination-phase contrast microscopic technique for 'in situ' analyses of DNA polymerase activities. Histochemistry. 1981; 71(4):567-79. DOI: 10.1007/BF00508382. View

11.

Lahn B, Page D . Retroposition of autosomal mRNA yielded testis-specific gene family on human Y chromosome. Nat Genet. 1999; 21(4):429-33. DOI: 10.1038/7771. View

12.

Reijo R, Lee T, Salo P, Alagappan R, Brown L, Rosenberg M . Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene. Nat Genet. 1995; 10(4):383-93. DOI: 10.1038/ng0895-383. View

13.

Christensen M, Rattner J, DIXON G . Hyperacetylation of histone H4 promotes chromatin decondensation prior to histone replacement by protamines during spermatogenesis in rainbow trout. Nucleic Acids Res. 1984; 12(11):4575-92. PMC: 318859. DOI: 10.1093/nar/12.11.4575. View

14.

Skaletsky H, Brown L, Minx P, Cordum H, Waterston R, Wilson R . The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men. Nat Genet. 2001; 29(3):279-86. DOI: 10.1038/ng757. View

15.

Grimes Jr S, Henderson N . Hyperacetylation of histone H4 in rat testis spermatids. Exp Cell Res. 1984; 152(1):91-7. DOI: 10.1016/0014-4827(84)90232-5. View

16.

Kleiman S, Lagziel A, Yogev L, Botchan A, Paz G, Yavetz H . Expression of CDY1 may identify complete spermatogenesis. Fertil Steril. 2001; 75(1):166-73. DOI: 10.1016/s0015-0282(00)01639-3. View

17.

Jenuwein T, Allis C . Translating the histone code. Science. 2001; 293(5532):1074-80. DOI: 10.1126/science.1063127. View

18.

Wykes S, Nelson J, Visscher D, Djakiew D, Krawetz S . Coordinate expression of the PRM1, PRM2, and TNP2 multigene locus in human testis. DNA Cell Biol. 1995; 14(2):155-61. DOI: 10.1089/dna.1995.14.155. View

19.

Parthun M, Widom J, Gottschling D . The major cytoplasmic histone acetyltransferase in yeast: links to chromatin replication and histone metabolism. Cell. 1996; 87(1):85-94. DOI: 10.1016/s0092-8674(00)81325-2. View

20.

Brownell J, Allis C . An activity gel assay detects a single, catalytically active histone acetyltransferase subunit in Tetrahymena macronuclei. Proc Natl Acad Sci U S A. 1995; 92(14):6364-8. PMC: 41518. DOI: 10.1073/pnas.92.14.6364. View