Previously uncharacterized histone acetyltransferases implicated in mammalian spermatogenesis.
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.
Lahn
Bruce T
BT
Howard Hughes Medical Institute, Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. blahn@genetics.uchicago.edu
Tang
Zhao Lan
ZL
Zhou
Jianxin
J
Barndt
Robert J
RJ
Parvinen
Martti
M
Allis
C David
CD
Page
David C
DC
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013087:Spermatids / Q000378:metabolism; D013091:Spermatogenesis / Q000502:physiology*
C118459:CDY1 protein, human; C485564:CDY2A protein, human; D017931:DNA Primers; D006657:Histones; D009687:Nuclear Proteins; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; D051548:Histone Acetyltransferases