Monovalent and unpoised status of most genes in undifferentiated cell-enriched Drosophila testis.
BACKGROUND
Increasing evidence demonstrates that stem cells maintain their identities by a unique transcription network and chromatin structure. Opposing epigenetic modifications H3K27 me3 and H3K4 me3 have been proposed to label differentiation-associated genes in stem cells, progenitor and precursor cells. In addition, many differentiation-associated genes are maintained at a poised status by recruitment of the initiative RNA Polymerase II (Pol II) at their promoter regions, in preparation for lineage-specific expression upon differentiation. Previous studies have been performed using cultured mammalian embryonic stem cells. To a lesser extent, chromatin structure has been delineated in other model organisms, such as Drosophila, to open new avenues for genetic analyses.


RESULTS
Here we use testes isolated from a Drosophila bag of marbles mutant strain, from which germ cells are in their undifferentiated status. We use these testes to study the endogenous chromatin structure of undifferentiated cells using ChIP-seq. We integrate the ChIP-seq with RNA-seq data, which measures the digital transcriptome. Our genome-wide analyses indicate that most differentiation-associated genes in undifferentiated cells lack an active chromatin mark and initiative Pol II; instead, they are associated with either the repressive H3K27 me3 mark or no detectable mark.


CONCLUSIONS
Our results reveal that most of the differentiation-associated genes in undifferentiated-cell-enriched Drosophila testes are associated with monovalent but not bivalent modifications, a chromatin signature that is distinct from the data reported in mammalian stem or precursor cells, which may reflect cell type specificity, species specificity, or both.
Gan
Qiang
Q
Department of Biology, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
Schones
Dustin E
DE
Ho Eun
Suk
S
Wei
Gang
G
Cui
Kairong
K
Zhao
Keji
K
Chen
Xin
X
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D017344:Genes, Insect; D008297:Male; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013737:Testis / Q000378:metabolism*
D002843:Chromatin; D029721:Drosophila Proteins
Curr Opin Genet Dev. 2006 Oct;16(5):455-62
16920351
Dev Cell. 2009 Sep;17(3):425-34
19758566
Cell. 2008 Feb 22;132(4):567-82
18295576
Development. 1997 Nov;124(21):4361-71
9334284
Nature. 2007 Aug 2;448(7153):553-60
17603471
Nature. 2000 Nov 30;408(6812):538-40
11117732
Dev Cell. 2008 May;14(5):798-809
18477461
Cell. 2007 Jul 13;130(1):77-88
17632057
Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11535-40
13679578
Science. 2008 Aug 15;321(5891):956-60
18599741
Genes Cells. 2001 Apr;6(4):291-301
11318872
Cell. 2002 Feb 22;108(4):489-500
11909520
Mech Dev. 2000 Jul;95(1-2):215-7
10906465
Development. 2007 Jan;134(2):223-32
17185323
Genes Dev. 1992 Feb;6(2):284-95
1737619
Cell Stem Cell. 2007 Sep 13;1(3):299-312
18371364
Development. 2004 Nov;131(21):5297-308
15456720
Cell. 2008 Feb 22;132(4):559-62
18295574
Science. 2002 Nov 1;298(5595):1039-43
12351676
J Cell Biochem. 2009 May 1;107(1):11-8
19173299
PLoS Genet. 2010 Jan;6(1):e1000805
20062800
Mol Cell. 2009 Jun 26;34(6):710-21
19560423
Annu Rev Genet. 2004;38:413-43
15568982
Cell. 2006 Apr 21;125(2):301-13
16630818
Mol Cell Biol. 1991 Mar;11(3):1508-22
1705007
Cell. 2002 Oct 18;111(2):197-208
12408864
Cell. 2006 Apr 21;125(2):233-6
16630812
PLoS Biol. 2009 Jan 13;7(1):e13
19143474
PLoS Biol. 2008 Dec 2;6(12):2911-27
19053175
Cell. 2006 Apr 21;125(2):315-26
16630819
Semin Cell Dev Biol. 1998 Aug;9(4):433-44
9813190
Nature. 2006 Feb 16;439(7078):871-4
16357870
Immunity. 2009 Jan 16;30(1):155-67
19144320
Nat Rev Genet. 2009 Jan;10(1):57-63
19015660
Nat Genet. 2007 Dec;39(12):1512-6
17994019
Nat Genet. 2007 Dec;39(12):1507-11
17994021
Cell Stem Cell. 2008 Jul 3;3(1):44-54
18593558
Cell. 2007 May 18;129(4):823-37
17512414
Biochem Biophys Res Commun. 2007 Feb 23;353(4):992-8
17214966
Genes Dev. 1990 Dec;4(12B):2242-51
2279698
Cell Stem Cell. 2007 Sep 13;1(3):286-98
18371363
Cell. 2008 Mar 7;132(5):887-98
18329373
Cell Res. 2010 Jul;20(7):763-83
20440302
Nat Methods. 2008 Jul;5(7):621-8
18516045
EMBO J. 2007 Apr 18;26(8):2041-51
17380126
Curr Opin Genet Dev. 2009 Apr;19(2):127-34
19299119
Bioinformatics. 2009 Aug 1;25(15):1952-8
19505939
Nat Rev Genet. 2008 Mar;9(3):179-91
18250624
Dev Biol. 2006 Jun 1;294(1):246-57
16616121
Science. 2005 Nov 4;310(5749):869-72
16272126
Nature. 2006 May 18;441(7091):349-53
16625203
PLoS Biol. 2010 Jan 05;8(1):e1000269
20076756
Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18207-12
19820169
EMBO Rep. 2004 Apr;5(4):373-7
15031712
Science. 2007 Apr 20;316(5823):402-4
17446390
Genes Dev. 2009 Jul 15;23(14):1606-12
19605681
Fly (Austin). 2008 Jan-Feb;2(1):19-28
18820440
Cell Stem Cell. 2009 Jan 9;4(1):80-93
19128795
Dev Cell. 2009 Sep;17(3):301-3
19758552
J Mol Biol. 2004 Aug 6;341(2):429-42
15276834
Development. 1995 Nov;121(11):3495-503
8582264
Nat Cell Biol. 2007 Dec;9(12):1428-35
18037880
Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):11940-5
10518555