Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa.
In higher eukaryotes, histone methylation is involved in maintaining cellular identity during somatic development. As most nucleosomes are replaced by protamines during spermatogenesis, it is unclear whether histone modifications function in paternal transmission of epigenetic information. Here we show that two modifications important for Trithorax- and Polycomb-mediated gene regulation have methylation-specific distributions at regulatory regions in human spermatozoa. Histone H3 Lys4 dimethylation (H3K4me2) marks genes that are relevant in spermatogenesis and cellular homeostasis. In contrast, histone H3 Lys27 trimethylation (H3K27me3) marks developmental regulators in sperm, as in somatic cells. However, nucleosomes are only moderately retained at regulatory regions in human sperm. Nonetheless, genes with extensive H3K27me3 coverage around transcriptional start sites in particular tend not to be expressed during male and female gametogenesis or in preimplantation embryos. Promoters of orthologous genes are similarly modified in mouse spermatozoa. These data are compatible with a role for Polycomb in repressing somatic determinants across generations, potentially in a variegating manner.
Brykczynska
Urszula
U
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Hisano
Mizue
M
Erkek
Serap
S
Ramos
Liliana
L
Oakeley
Edward J
EJ
Roloff
Tim C
TC
Beisel
Christian
C
Schübeler
Dirk
D
Stadler
Michael B
MB
Peters
Antoine H F M
AH
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D019175:DNA Methylation; D019143:Evolution, Molecular; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008745:Methylation; D051379:Mice; D051788:Myeloid-Lymphoid Leukemia Protein / Q000378:metabolism; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D063146:Polycomb-Group Proteins; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D013045:Species Specificity; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology; D013094:Spermatozoa / Q000378:metabolism*; D014158:Transcription, Genetic
D006657:Histones; C497422:KMT2A protein, human; D009707:Nucleosomes; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase
EMBO J. 1998 Aug 17;17(16):4887-902
9707448
Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):14976-80
18799751
J Cell Sci. 1998 Aug;111 ( Pt 15):2227-34
9664044
Cell Stem Cell. 2007 Sep 13;1(3):299-312
18371364
Cell. 2009 Mar 20;136(6):1122-35
19303854
Curr Biol. 2006 Apr 4;16(7):660-7
16581510
Nat Cell Biol. 2008 Jan;10(1):102-9
18066050
Nat Genet. 2009 May;41(5):563-71
19377475
Methods Mol Biol. 2004;287:99-120
15273407
Nat Genet. 2007 May;39(5):614-22
17450140
Cell Differ. 1977 Mar;5(5-6):343-55
856479
Science. 2002 Nov 1;298(5595):1039-43
12351676
BMC Dev Biol. 2006 Jul 21;6:34
16859545
Dev Biol. 2005 Jul 1;283(1):40-57
15975430
Nature. 2004 Jun 24;429(6994):900-3
15215868
Mol Cell. 2008 Nov 21;32(4):491-502
19026780
Curr Opin Genet Dev. 2004 Dec;14(6):692-6
15531166
Int J Dev Biol. 2006;50(5):455-61
16586346
J Cell Biol. 2000 Dec 25;151(7):1591-8
11134086
Nature. 2007 May 24;447(7143):425-32
17522676
Cell. 2009 Apr 17;137(2):308-20
19379696
EMBO Rep. 2005 Aug;6(8):748-54
16007070
Genes Dev. 2006 May 1;20(9):1123-36
16618801
Nature. 2007 Aug 2;448(7153):553-60
17603471
Genes Dev. 2002 Nov 15;16(22):2893-905
12435631
Hum Reprod. 2008 Feb;23(2):259-70
18056059
PLoS Genet. 2008 Oct;4(10):e1000242
18974828
Int J Dev Biol. 2009;53(2-3):335-54
19412890
Development. 2009 Nov;136(21):3531-42
19820181
Mol Cell. 2008 Jun 20;30(6):755-66
18514006
Mol Reprod Dev. 2009 Jan;76(1):101-8
18481364
Nat Rev Cancer. 2006 Nov;6(11):846-56
17060944
J Biol Chem. 2003 Aug 8;278(32):29471-7
12775710
Nat Genet. 2008 Apr;40(4):411-20
18311137
Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12451-5
8618919
J Cell Sci. 1999 Oct;112 ( Pt 20):3537-48
10504302
Nat Biotechnol. 2007 Sep;25(9):1045-50
17704765
Proc Natl Acad Sci U S A. 2007 May 15;104(20):8346-51
17483452
Nature. 2009 Jul 23;460(7254):473-8
19525931
Nat Genet. 2006 Dec;38(12):1440-5
17099714
Nature. 2009 Oct 8;461(7265):762-7
19767730
N Engl J Med. 2003 Jul 17;349(3):275-86
12867612
Cell Stem Cell. 2007 Sep 13;1(3):286-98
18371363
Biol Reprod. 2003 Dec;69(6):1815-21
12890724
Nature. 2006 Sep 7;443(7107):101-5
16943775
Mol Cell Biol. 1998 Jun;18(6):3350-6
9584175
Nat Genet. 2007 Apr;39(4):457-66
17334365
J Reprod Dev. 2007 Aug;53(4):707-15
17827882
BMC Dev Biol. 2008 Mar 31;8:34
18377649
Nat Cell Biol. 2008 Nov;10(11):1291-300
18931660
Curr Opin Genet Dev. 2009 Apr;19(2):113-21
19359161
Dev Biol. 2005 Oct 15;286(2):493-506
16168984
Biotechniques. 2006 Nov;41(5):577-80
17140114
Nat Cell Biol. 2008 Nov;10(11):1280-90
18836439
Genome Res. 2009 Aug;19(8):1338-49
19584098
Development. 2005 May;132(9):2093-102
15788452
Mech Dev. 2005 Sep;122(9):1008-22
15922569
Curr Opin Cell Biol. 2007 Jun;19(3):257-65
17467256
Science. 1987 May 22;236(4804):962-4
3576213
Biochemistry. 1977 Sep 6;16(18):4074-80
911755