TY - JOUR
T1 - Alteration of poly(ADP-ribose) metabolism affects murine sperm nuclear architecture by impairing pericentric heterochromatin condensation
AU - Meyer-Ficca, Mirella L.
AU - Lonchar, Julia D.
AU - Ihara, Motomasa
AU - Bader, Jessica J.
AU - Meyer, Ralph G.
N1 - Funding Information:
Acknowledgments This work was supported by grants from the National Institutes of Health (NIH R01HD048837 and U54HD068157) and the Mari Lowe Center for Comparative Oncology at the University of Pennsylvania. We are grateful to Dr. Lingli Zhang and Dr. Gordon Ruthel (University of Pennsylvania, School of Veterinary Medicine Imaging Facility) for the help with confocal microscopy and to Dr. Larry L Laster and to the University of Pennsylvania’s Center for Clinical Epidemiology and Biostatistics for the help with the statistical analyses.
PY - 2013/8
Y1 - 2013/8
N2 - 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.
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.
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U2 - 10.1007/s00412-013-0416-y
DO - 10.1007/s00412-013-0416-y
M3 - Article
C2 - 23729169
AN - SCOPUS:84880795001
SN - 0009-5915
VL - 122
SP - 319
EP - 335
JO - Chromosoma
JF - Chromosoma
IS - 4
ER -