Poly(ADP-ribose) metabolism is essential for proper nucleoprotein exchange during mouse spermiogenesis.
Sperm chromatin is organized in a protamine-based, highly condensed form, which protects the paternal chromosome complement in transit, facilitates fertilization, and supports correct gene expression in the early embryo. Very few histones remain selectively associated with genes and defined regulatory sequences essential to embryonic development, while most of the genome becomes bound to protamine during spermiogenesis. Chromatin remodeling processes resulting in the dramatically different nuclear structure of sperm are poorly understood. This study shows that perturbation of poly(ADP-ribose) (PAR) metabolism, which is mediated by PAR polymerases and PAR glycohydrolase in response to naturally occurring endogenous DNA strand breaks during spermatogenesis, results in the abnormal retention of core histones and histone linker HIST1H1T (H1t) and H1-like linker protein HILS1 in mature sperm. Moreover, genetic or pharmacological alteration of PAR metabolism caused poor sperm chromatin quality and an abnormal nuclear structure in mice, thus reducing male fertility.
Meyer-Ficca
Mirella L
ML
Department of Animal Biology and Mari Lowe Center for Comparative Oncology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania 19104, USA.
Ihara
Motomasa
M
Lonchar
Julia D
JD
Meistrich
Marvin L
ML
Austin
Caroline A
CA
Min
Wookee
W
Wang
Zhao-Qi
ZQ
Meyer
Ralph G
RG
D000818:Animals; D030801:Animals, Genetically Modified; D002467:Cell Nucleus / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000502:physiology; D053960:DNA Breaks; D004268:DNA-Binding Proteins / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008297:Male; D051379:Mice; D009698:Nucleoproteins / Q000378:metabolism*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013087:Spermatids / Q000502:physiology; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa / Q000378:metabolism
D004268:DNA-Binding Proteins; C494057:Hils1 protein, mouse; D006657:Histones; D009698:Nucleoproteins; D011064:Poly Adenosine Diphosphate Ribose; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase