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GENES & DEVELOPMENT 20:2580-2592, 2006
©2006 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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Phosphorylation of histone H4 Ser1 regulates sporulation in yeast and is conserved in fly and mouse spermatogenesis

Thanuja Krishnamoorthy1, Xin Chen2, Jerome Govin3, Wang L. Cheung4,7, Jean Dorsey1, Karen Schindler5, Edward Winter5, C. David Allis4,8, Vincent Guacci6, Saadi Khochbin3, Margaret T. Fuller2 and Shelley L. Berger1,9

1 Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA; 2 Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA; 3 Institut National de la Santé et de la Recherche Médicale (INSERM) U309, Institut Albert Bonniot Faculté de Médecine, 38706 La Tronche, France; 4 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22908, USA; 5 Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA; 6 Department of Embryology, Howard Hughes Medical Institute/Carnegie Institution, Baltimore, Maryland 21218, USA

Sporulation in Saccharomyces cerevisiae is a highly regulated process wherein a diploid cell gives rise to four haploid gametes. In this study we show that histone H4 Ser1 is phosphorylated (H4 S1ph) during sporulation, starting from mid-sporulation and persisting to germination, and is temporally distinct from earlier meiosis-linked H3 S10ph involved in chromosome condensation. A histone H4 S1A substitution mutant forms aberrant spores and has reduced sporulation efficiency. Deletion of sporulation-specific yeast Sps1, a member of the Ste20 family of kinases, nearly abolishes the sporulation-associated H4 S1ph modification. H4 S1ph may promote chromatin compaction, since deletion of SPS1 increases accessibility to antibody immunoprecipitation; furthermore, either deletion of Sps1 or an H4 S1A substitution results in increased DNA volume in nuclei within spores. We find H4 S1ph present during Drosophila melanogaster and mouse spermatogenesis, and similar to yeast, this modification extends late into sperm differentiation relative to H3 S10ph. Thus, H4 S1ph may be an evolutionarily ancient histone modification to mark the genome for gamete-associated packaging.

[Keywords: Saccharomyces cerevisiae ; fly and mouse spermatogenesis; genome compaction; histone H4 phosphorylation; kinase; yeast sporulation]

Received June 8, 2006; revised version accepted July 25, 2006.


7 Present Addresses: Department of Pathology, Johns Hopkins Hospital, Baltimore, MD 21287, USA;

8 Laboratory of Chromatin Biology, The Rockefeller University, New York, NY 10021, USA.

9 Corresponding author.

E-MAIL berger{at}wistar.org; FAX (215) 898-0663.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1457006.


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