Institute for Biogenesis Research Dept. Anatomy, Biochemistry & Physiology Chief, Research Division Lakshmi Devi and Devraj Sharma Endowed Chair
Affiliation: Institute for Biogenesis Research Department of Anatomy Biochemistry and Physiology John A. Burns School of Medicine University of Hawaii
Graduate Faculty: Developmental and Reproductive Biology (DRB) Cell and Molecular Biology (CMB)
Phone: (808) 956-5189
Fax: (808) 956-7316
Email: wward@hawaii.edu
Address: IBR, 1960 East-West Rd, Room E108, Honolulu, HI 96822
The function and structure of mammalian sperm chromatin
Description Of Research
Our research is focused on the structure of mammalian sperm chromatin and how this is related to function. The main hypothesis that we have tested is that the sperm cell provided the newly developing embryo with more than just the genetic code in the DNA sequence; it also provides a three dimensional organization of the DNA that provides crucial information as to how to use the father’s genetic code.
DNA is packaged very densely in the sperm nucleus in a manner that is different from any other cell type. Most of the histones are replaced by protamines, and the DNA is crystallized into dense toroids with roughly 50,000 bp of DNA, each. Protamine condensation protects the sperm DNA from damage from external insults, and prevents transcription or DNA replication from occurring. We have shown that one structural feature present in all other somatic cells is also retained in sperm chromatin – the organization of DNA into loop domains attached at their bases to the nuclear matrix.
This organization is crucial to two aspects of sperm chromatin function. Shortly after fertilization, the protamines are removed from the sperm DNA and the chromatin is repackaged with histones. The DNA is then replicated, and we have demonstrated that this DNA synthesis requires the loop domain organization to be intact. On the other hand, spermatozoa have the ability to digest their own DNA through an apoptotic-like process in which the sperm DNA is degraded. This degradation occurs on the nuclear matrix.
Our current research efforts are focused on understanding how sperm chromatin structure is related to the events that occur shortly after fertilization and how the DNA packaging in the sperm cell contributes to embryonic development.
Selected Publications
Nadel B, de Lara J, Finkernagel SW, Ward WS. Cell-specific organization of the 5S ribosomal RNA gene cluster DNA loop domains in spermatozoa and somatic cells. Biology of Reproduction 1995; 53: 1222-1228. PMID: PMID: 8527528
Shaman JA, Yamauchi Y, Ward WS. The Sperm Nuclear Matrix is Required for Paternal DNA Replication. J Cell Biochem 2007; 102: 680-688. PMID: PMID: 17415751
Yamauchi Y, Shaman JA, Ward WS. Topoisomerase II Mediated Breaks in Spermatozoa Cause the Specific Degradation of Paternal DNA in Fertilized Oocytes. Biology of Reproduction 2007; 76: 666-672. PMID: PMID: 17182890;
Ward WS. Function of sperm chromatin structural elements in fertilization and development. Mol Hum Reprod 2010; 16: 30-36. PMID: PMID: 19748904 PMCID: PMC2790366; 2790366
Nguyen H, James NG, Nguyen L, Nguyen TP, Vuong C, Ortega MA, Jameson DM, Ward WS. Higher order oligomerization of the licensing ORC4 protein is required for polar body extrusion in murine meiosis. J Cell Biochem 2017; In Press. PMID: 28230328