Transition nuclear proteins are required for normal chromatin condensation and functional sperm development.
The histone-to-protamine transition is important in the formation of spermatozoa. In mammals this involves two steps: replacement of histones by transition nuclear proteins (TPs) and replacement of TPs by protamines. To determine the functions of the TPs and their importance for sperm development, we generated mice lacking both TPs, since mice lacking only TP1 or TP2 were fertile. Our results indicated that TP1 and TP2 had partially complemented each other. In mice lacking both TPs, nuclear shaping, transcriptional repression, histone displacement, and protamine deposition proceeded relatively normally, but chromatin condensation was irregular in all spermatids, many late spermatids showed DNA breaks, and protamine 2 was not posttranslationally processed. Nevertheless, genomic integrity was maintained in mature spermatids, since efficient fertilization and production of offspring were achieved by intracytoplasmic sperm injection. However, many mature spermatids were retained in the testis, epididymal spermatozoa were drastically reduced in number and were highly abnormal, and the mice were sterile. Most epididymal spermatozoa were incapable of fertilization even using intracytoplasmic sperm injection. Thus, in mammals TPs are required for normal chromatin condensation, for reducing the number of DNA breaks, and for preventing the formation of secondary defects in spermatozoa, eventual loss of genomic integrity, and sterility.
Zhao
Ming
M
Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Shirley
Cynthia R
CR
Hayashi
Shotaro
S
Marcon
Ludovic
L
Mohapatra
Bhagyalaxmi
B
Suganuma
Ryota
R
Behringer
Richard R
RR
Boissonneault
Guylain
G
Yanagimachi
Ryuzo
R
Meistrich
Marvin L
ML
D000375:Aging / Q000502:physiology; D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016678:Genome; D006657:Histones / Q000378:metabolism; D007248:Infertility, Male / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009154:Mutation / Q000235:genetics; D011479:Protamines / Q000378:metabolism; D013091:Spermatogenesis; D013094:Spermatozoa / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D011479:Protamines; C053886:spermatid transition proteins