Stability and dynamics of polycomb target sites in Drosophila development.
Polycomb-group (PcG) and Trithorax-group proteins together form a maintenance machinery that is responsible for stable heritable states of gene activity. While the best-studied target genes are the Hox genes of the Antennapedia and Bithorax complexes, a large number of key developmental genes are also Polycomb (Pc) targets, indicating a widespread role for this maintenance machinery in cell fate determination. We have studied the linkage between the binding of PcG proteins and the developmental regulation of gene expression using whole-genome mapping to identify sites bound by the PcG proteins, Pc and Pleiohomeotic (Pho), in the Drosophila embryo and in a more restricted tissue, the imaginal discs of the third thoracic segment. Our data provide support for the idea that Pho is a general component of the maintenance machinery, since the majority of Pc targets are also associated with Pho binding. We find, in general, considerable developmental stability of Pc and Pho binding at target genes and observe that Pc/Pho binding can be associated with both expressed and inactive genes. In particular, at the Hox complexes, both active and inactive genes have significant Pc and Pho binding. However, in comparison to inactive genes, the active Hox genes show reduced and altered binding profiles. During development, Pc target genes are not simply constantly associated with Pc/Pho binding, and we identify sets of genes with clear differential binding between embryo and imaginal disc. Using existing datasets, we show that for specific fate-determining genes of the haemocyte lineage, the active state is characterised by lack of Pc binding. Overall, our analysis suggests a dynamic relationship between Pc/Pho binding and gene transcription. Pc/Pho binding does not preclude transcription, but levels of Pc/Pho binding change during development, and loss of Pc/Pho binding can be associated with both stable gene activity and inactivity.
Kwong
Camilla
C
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Adryan
Boris
B
Bell
Ian
I
Meadows
Lisa
L
Russell
Steven
S
Manak
J Robert
JR
White
Robert
R
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology* / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C113295:pho protein, Drosophila
Nature. 1989 Feb 2;337(6206):468-71
2563569
Mech Dev. 2005 Sep;122(9):975-87
16024236
Dev Cell. 2002 Nov;3(5):659-71
12431373
Genes Dev. 2005 Aug 1;19(15):1755-60
16077005
Nucleic Acids Res. 2005 Sep 09;33(16):5181-9
16155187
Cell. 2007 Feb 23;128(4):735-45
17320510
Mol Cell Biol. 2002 Nov;22(21):7473-83
12370294
Genes Dev. 2006 Aug 1;20(15):2041-54
16882982
Genes Dev. 2002 Oct 15;16(20):2672-83
12381666
Mol Cell Biol. 2006 Feb;26(4):1434-44
16449654
Curr Opin Cell Biol. 2004 Dec;16(6):700-7
15530784
Nature. 2002 Apr 11;416(6881):644-8
11912489
Nat Genet. 2006 Oct;38(10):1151-8
16951679
Cell. 2006 Dec 15;127(6):1209-21
17174895
EMBO J. 2004 Feb 25;23(4):857-68
14963490
Mol Cell. 1998 Jun;1(7):1057-64
9651589
EMBO J. 1995 May 1;14(9):2056-65
7744011
Dev Cell. 2003 Nov;5(5):759-71
14602076
EMBO J. 1998 Sep 1;17(17):5141-50
9724650
Nat Genet. 2006 Jun;38(6):700-5
16732288
BMC Bioinformatics. 2008 Mar 20;9:157
18366701
Mol Cell. 2004 Nov 19;16(4):641-53
15546623
Development. 2005 Sep;132(17):3963-76
16079157
Annu Rev Genet. 2004;38:413-43
15568982
Cell. 2006 Apr 21;125(2):301-13
16630818
Genes Dev. 2006 May 1;20(9):1123-36
16618801
Nature. 2001 Aug 9;412(6847):655-60
11493925
Nat Cell Biol. 2006 May;8(5):532-8
16570078
Nature. 2007 Aug 2;448(7153):553-60
17603471
Nucleic Acids Res. 2005 Mar 10;33(5):1445-53
15760844
Development. 1990 Jul;109(3):553-66
1976090
Chromosoma. 1999 May;108(2):83-94
10382070
Development. 1997 Nov;124(21):4343-50
9334282
Bioinformatics. 2004 Nov 22;20(17):3246-8
15180930
Cell Microbiol. 2007 May;9(5):1117-26
17394559
Cell. 2007 Jun 29;129(7):1311-23
17604720
Cell. 2006 Apr 21;125(2):315-26
16630819
Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16615-20
17921257
Genes Dev. 2006 May 1;20(9):1110-22
16618800
Development. 1999 Sep;126(17):3905-13
10433918
Genes Dev. 2006 Feb 15;20(4):501-13
16481477
Bioinformatics. 2002 Jan;18(1):207-8
11836235
Development. 2001 Mar;128(6):993-1004
11222153
Genome Biol. 2005;6(7):R63
15998452
Mol Cell Biol. 2001 Feb;21(4):1311-8
11158316
Nature. 2005 Mar 24;434(7032):533-8
15791260
Genetics. 1997 Aug;146(4):1365-80
9258680
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8
9843981
Development. 1988 Dec;104(4):713-20
2908325
EMBO J. 1985 Aug;4(8):2035-43
16453630
PLoS Biol. 2006 Jun;4(6):e170
16613483
Nat Genet. 2007 Jun;39(6):715-20
17534367
Science. 2003 Apr 4;300(5616):131-5
12649488
Nat Genet. 2006 Jun;38(6):694-9
16628213
Nature. 2006 May 18;441(7091):349-53
16625203
Mol Cell Biol. 1986 Dec;6(12):4667-75
2879222
Development. 2003 Jan;130(2):285-94
12466196
Genetics. 1996 Jun;143(2):913-28
8725238
Mol Cell. 2004 Jun 4;14(5):637-46
15175158
Development. 2001 Jun;128(11):2163-73
11493537