PMID- 23729169 OWN - NLM STAT- MEDLINE DCOM- 20140131 LR - 20211021 IS - 1432-0886 (Electronic) IS - 0009-5915 (Print) IS - 0009-5915 (Linking) VI - 122 IP - 4 DP - 2013 Aug TI - Alteration of poly(ADP-ribose) metabolism affects murine sperm nuclear architecture by impairing pericentric heterochromatin condensation. PG - 319-35 LID - 10.1007/s00412-013-0416-y [doi] AB - The mammalian sperm nucleus is characterized by unique properties that are important for fertilization. Sperm DNA retains only small numbers of histones in distinct positions, and the majority of the genome is protamine associated, which allows for extreme condensation and protection of the genetic material. Furthermore, sperm nuclei display a highly ordered architecture that is characterized by a centrally located chromocenter comprising the pericentromeric chromosome regions and peripherally positioned telomeres. Establishment of this unique and well-conserved nuclear organization during spermiogenesis is not well understood. Utilizing fluorescence in situ hybridization (FISH), we show that a large fraction of the histone-associated sperm genome is repetitive in nature, while a smaller fraction is associated with unique DNA sequences. Coordinated activity of poly(ADP-ribose) (PAR) polymerase and topoisomerase II beta has been shown to facilitate DNA relaxation and histone to protamine transition during spermatid condensation, and altered PAR metabolism is associated with an increase in sperm histone content. Combining FISH with three-dimensional laser scanning microscopy technology, we further show that altered PAR metabolism by genetic or pharmacological intervention leads to a disturbance of the overall sperm nuclear architecture with a lower degree of organization and condensation of the chromocenters formed by chromosomal pericentromeric heterochromatin. FAU - Meyer-Ficca, Mirella L AU - Meyer-Ficca ML AD - Center for Animal Transgenesis and Germ Cell Research, Department of Animal Biology and Mari Lowe Center for Comparative Oncology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA. FAU - Lonchar, Julia D AU - Lonchar JD FAU - Ihara, Motomasa AU - Ihara M FAU - Bader, Jessica J AU - Bader JJ FAU - Meyer, Ralph G AU - Meyer RG LA - eng GR - U54 HD068157/HD/NICHD NIH HHS/United States GR - R01 HD048837/HD/NICHD NIH HHS/United States GR - U54HD068157/HD/NICHD NIH HHS/United States GR - P50 HD068157/HD/NICHD NIH HHS/United States GR - R01HD048837/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20130601 PL - Austria TA - Chromosoma JT - Chromosoma JID - 2985138R RN - 0 (Heterochromatin) RN - 0 (Histones) RN - 26656-46-2 (Poly Adenosine Diphosphate Ribose) RN - 9007-49-2 (DNA) RN - EC 2.4.2.30 (Parp1 protein, mouse) RN - EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1) RN - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases) SB - IM MH - Animals MH - Cell Nucleus/genetics/*metabolism MH - *Chromatin Assembly and Disassembly MH - DNA/genetics/metabolism MH - Heterochromatin/*metabolism MH - Histones/metabolism MH - Male MH - Mice/genetics/*metabolism MH - Mice, Knockout MH - Poly (ADP-Ribose) Polymerase-1 MH - Poly Adenosine Diphosphate Ribose/*metabolism MH - Poly(ADP-ribose) Polymerases/genetics/metabolism MH - Spermatogenesis MH - Spermatozoa/cytology/*metabolism PMC - PMC3762462 MID - NIHMS487717 EDAT- 2013/06/05 06:00 MHDA- 2014/02/01 06:00 PMCR- 2014/08/01 CRDT- 2013/06/05 06:00 PHST- 2013/03/12 00:00 [received] PHST- 2013/05/13 00:00 [accepted] PHST- 2013/05/07 00:00 [revised] PHST- 2013/06/05 06:00 [entrez] PHST- 2013/06/05 06:00 [pubmed] PHST- 2014/02/01 06:00 [medline] PHST- 2014/08/01 00:00 [pmc-release] AID - 10.1007/s00412-013-0416-y [doi] PST - ppublish SO - Chromosoma. 2013 Aug;122(4):319-35. doi: 10.1007/s00412-013-0416-y. Epub 2013 Jun 1.