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Previously uncharacterized histone acetyltransferases implicated in mammalian spermatogenesis
Bruce T Lahn1, Zhao Lan Tang, Jianxin Zhou
1Howard Hughes Medical Institute, Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. blahn@genetics.uchicago.edu
Summary
Human CDY and mouse CDYL proteins are histone acetyltransferases that facilitate histone removal during sperm development. This finding explains male infertility linked to CDY gene deletions.
Area of Science:
- Molecular Biology
- Reproductive Biology
- Genetics
Background:
- During spermiogenesis, histones are replaced by protamines for DNA packaging.
- Histone H4 hyperacetylation is thought to facilitate this transition.
- The specific enzymes responsible for H4 hyperacetylation remained unidentified.
Purpose of the Study:
- To identify the histone acetyltransferase enzymes involved in histone-to-protamine transition.
- To investigate the role of CDY and its mouse homolog CDYL in spermiogenesis.
- To explore the link between CDY gene function and male infertility.
Main Methods:
- In vitro assays to determine histone acetyltransferase activity of human CDY and mouse CDYL.
- Analysis of human CDY and mouse Cdyl gene expression during spermatogenesis.
- Immunolocalization studies of CDY and CDYL proteins in maturing spermatids.
Main Results:
- Human CDY and mouse CDYL proteins exhibit in vitro histone acetyltransferase activity, preferentially on histone H4.
- Expression of CDY and Cdyl genes correlates with H4 hyperacetylation during spermatogenesis.
- CDY and CDYL proteins localize to the nuclei of maturing spermatids where H4 hyperacetylation occurs.
Conclusions:
- Human CDY and mouse CDYL are identified as key enzymes in the histone-to-protamine transition during mammalian spermiogenesis.
- These findings provide a molecular mechanism linking CDY gene function to male fertility.
- CDY gene deletions may cause spermatogenic failure due to impaired H4 hyperacetylation.