Loss of the cleaved-protamine 2 domain leads to incomplete histone-to-protamine exchange and infertility in mice.
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
13
10
2021
accepted:
24
05
2022
revised:
11
07
2022
pubmed:
29
6
2022
medline:
14
7
2022
entrez:
28
6
2022
Statut:
epublish
Résumé
Protamines are unique sperm-specific proteins that package and protect paternal chromatin until fertilization. A subset of mammalian species expresses two protamines (PRM1 and PRM2), while in others PRM1 is sufficient for sperm chromatin packaging. Alterations of the species-specific ratio between PRM1 and PRM2 are associated with infertility. Unlike PRM1, PRM2 is generated as a precursor protein consisting of a highly conserved N-terminal domain, termed cleaved PRM2 (cP2), which is consecutively trimmed off during chromatin condensation. The carboxyterminal part, called mature PRM2 (mP2), interacts with DNA and together with PRM1, mediates chromatin-hypercondensation. The removal of the cP2 domain is believed to be imperative for proper chromatin condensation, yet, the role of cP2 is not yet understood. We generated mice lacking the cP2 domain while the mP2 is still expressed. We show that the cP2 domain is indispensable for complete sperm chromatin protamination and male mouse fertility. cP2 deficient sperm show incomplete protamine incorporation and a severely altered protamine ratio, retention of transition proteins and aberrant retention of the testis specific histone variant H2A.L.2. During epididymal transit, cP2 deficient sperm seem to undergo ROS mediated degradation leading to complete DNA fragmentation. The cP2 domain therefore seems to be a key aspect in the complex crosstalk between histones, transition proteins and protamines during sperm chromatin condensation. Overall, we present the first step towards understanding the role of the cP2 domain in paternal chromatin packaging and open up avenues for further research.
Identifiants
pubmed: 35763544
doi: 10.1371/journal.pgen.1010272
pii: PGENETICS-D-21-01373
pmc: PMC9273070
doi:
Substances chimiques
Chromatin
0
Histones
0
Protamines
0
protamine 2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1010272Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Hum Reprod. 2006 Aug;21(8):2084-9
pubmed: 16632464
Biol Reprod. 2019 May 1;100(5):1250-1260
pubmed: 30753283
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nat Biotechnol. 2013 Sep;31(9):827-32
pubmed: 23873081
Mol Reprod Dev. 2002 Apr;61(4):519-27
pubmed: 11891924
Mol Hum Reprod. 2022 Feb 4;28(2):
pubmed: 35150275
Biochem Biophys Res Commun. 1998 Nov 27;252(3):602-9
pubmed: 9837753
Biol Reprod. 2016 Jul;95(1):4
pubmed: 27170439
Eur J Biochem. 1993 Jun 1;214(2):609-15
pubmed: 8513810
Sci Rep. 2016 Nov 11;6:36764
pubmed: 27833122
Nucleic Acids Res. 2017 Jan 4;45(D1):D183-D189
pubmed: 27899595
Biochem Int. 1988 Oct;17(4):701-10
pubmed: 3240317
Mol Cell Biol. 1987 Jun;7(6):2173-9
pubmed: 3600661
Fertil Steril. 1998 Apr;69(4):755-9
pubmed: 9548169
Nat Methods. 2004 Dec;1(3):249-54
pubmed: 16144087
Cell Rep. 2015 Dec 1;13(9):1765-71
pubmed: 26628361
FEBS Lett. 1999 Jan 15;442(2-3):189-92
pubmed: 9928999
J Proteome Res. 2008 Jan;7(1):29-34
pubmed: 18067246
Hum Reprod. 2008 Jan;23(1):11-6
pubmed: 18003625
Biol Reprod. 2004 Oct;71(4):1220-9
pubmed: 15189834
Nat Commun. 2014 Jun 26;5:4240
pubmed: 24967838
Nucleic Acids Res. 2010 Apr;38(6):1780-9
pubmed: 20008104
Nat Biotechnol. 2015 Mar;33(3):290-5
pubmed: 25690850
Nat Methods. 2013 Aug;10(8):730-6
pubmed: 23921808
Cells. 2020 Jul 27;9(8):
pubmed: 32727081
Genesis. 2004 Apr;38(4):200-13
pubmed: 15083521
Cell Mol Life Sci. 2005 Feb;62(3):344-54
pubmed: 15723169
Biochim Biophys Acta. 2014 Mar;1839(3):155-68
pubmed: 24091090
Sci Rep. 2017 Apr 07;7:46228
pubmed: 28387373
Protein Pept Lett. 2011 Aug;18(8):778-85
pubmed: 21443491
Fertil Steril. 2011 Jan;95(1):105-9
pubmed: 20667534
Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4683-8
pubmed: 10781074
Biol Reprod. 2014 Mar 27;90(3):67
pubmed: 24522148
Mol Cell Biol. 2001 Nov;21(21):7243-55
pubmed: 11585907
Nat Commun. 2016 Jan 20;7:10431
pubmed: 26786405
J Cell Biol. 2007 Jan 29;176(3):283-94
pubmed: 17261847
Prog Nucleic Acid Res Mol Biol. 1991;40:25-94
pubmed: 2031084
Nat Biotechnol. 2011 Jan;29(1):24-6
pubmed: 21221095
Proc Biol Sci. 2014 Mar 26;281(1783):20133359
pubmed: 24671975
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
PLoS One. 2011;6(12):e29247
pubmed: 22216223
Cells. 2020 Feb 18;9(2):
pubmed: 32085641
Biol Reprod. 2004 Sep;71(3):1016-25
pubmed: 15163613
BMC Evol Biol. 2011 Jan 13;11:12
pubmed: 21232104
Genome Biol. 2007;8(9):227
pubmed: 17903313
Eur J Biochem. 1992 Mar 1;204(2):759-65
pubmed: 1541289
Asian J Androl. 2003 Dec;5(4):315-24
pubmed: 14695982
Development. 2022 Jun 15;149(12):
pubmed: 35608054
J Mol Evol. 1988;27(4):291-7
pubmed: 3146639
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
Protein Pept Lett. 2018;25(5):424-433
pubmed: 29651936
Mol Cell. 2017 Apr 6;66(1):89-101.e8
pubmed: 28366643
BMC Evol Biol. 2016 Jan 22;16:21
pubmed: 26801756
Reproduction. 2002 Oct;124(4):491-9
pubmed: 12361467