JIL-1 and Su(var)3-7 interact genetically and counteract each other's effect on position-effect variegation in Drosophila.
The essential JIL-1 histone H3S10 kinase is a key regulator of chromatin structure that functions to maintain euchromatic domains while counteracting heterochromatization and gene silencing. In the absence of the JIL-1 kinase, two of the major heterochromatin markers H3K9me2 and HP1a spread in tandem to ectopic locations on the chromosome arms. Here we address the role of the third major heterochromatin component, the zinc-finger protein Su(var)3-7. We show that the lethality but not the chromosome morphology defects associated with the null JIL-1 phenotype to a large degree can be rescued by reducing the dose of the Su(var)3-7 gene and that Su(var)3-7 and JIL-1 loss-of-function mutations have an antagonistic and counterbalancing effect on position-effect variegation (PEV). Furthermore, we show that in the absence of JIL-1 kinase activity, Su(var)3-7 gets redistributed and upregulated on the chromosome arms. Reducing the dose of the Su(var)3-7 gene dramatically decreases this redistribution; however, the spreading of H3K9me2 to the chromosome arms was unaffected, strongly indicating that ectopic Su(var)3-9 activity is not a direct cause of lethality. These observations suggest a model where Su(var)3-7 functions as an effector downstream of Su(var)3-9 and H3K9 dimethylation in heterochromatic spreading and gene silencing that is normally counteracted by JIL-1 kinase activity.
Deng
Huai
H
Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, Iowa 50011, USA.
Cai
Weili
W
Wang
Chao
C
Lerach
Stephanie
S
Delattre
Marion
M
Girton
Jack
J
Johansen
Jørgen
J
Johansen
Kristen M
KM
D000818:Animals; D030801:Animals, Genetically Modified; D055012:Chromosomal Position Effects; D059006:Chromosomes, Insect / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D004843:Epistasis, Genetic; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D007150:Immunohistochemistry; D008239:Lysine / Q000378:metabolism; D008297:Male; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics; D008856:Microscopy, Fluorescence; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006657:Histones; C449619:Su(var)3-7 protein, Drosophila; D049452:Green Fluorescent Proteins; D008780:Methyltransferases; C445404:SU(VAR)3-9; C507306:JIL-1 protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D008239:Lysine
Methods. 2009 Aug;48(4):387-97
19272452
Nature. 2001 Mar 1;410(6824):116-20
11242053
Curr Opin Genet Dev. 2000 Apr;10(2):204-10
10753776
Chromosoma. 2005 Aug;114(3):173-82
15986206
Genes Dev. 2003 Nov 15;17(22):2825-38
14630943
Nature. 1990 Mar 15;344(6263):219-23
2107402
Mol Cell. 2007 Apr 13;26(1):103-15
17434130
Mol Cell. 1999 Jul;4(1):129-35
10445035
Annu Rev Genet. 1995;29:577-605
8825487
Genetics. 2007 Jun;176(2):1355-8
17435241
Chromosoma. 1998 Nov;107(5):277-85
9880760
Chromosoma. 2006 Apr;115(2):139-50
16463146
Genetics. 2006 Aug;173(4):2403-6
16702418
J Cell Sci. 2005 Nov 1;118(Pt 21):5047-57
16234327
Genetics. 2007 Sep;177(1):79-87
17660558
Curr Opin Genet Dev. 2002 Apr;12(2):178-87
11893491
Development. 2004 Aug;131(15):3571-80
15215206
J Cell Sci. 2004 Dec 1;117(Pt 25):6239-47
15564384
EMBO J. 2002 Mar 1;21(5):1121-31
11867540
Adv Genet. 2008;61:1-43
18282501
Proc Natl Acad Sci U S A. 1936 Jan;22(1):27-33
16588038
Chromosome Res. 2006;14(4):393-404
16821135
Genes Dev. 1995 May 15;9(10):1263-77
7758950
Genes Dev. 2004 Dec 1;18(23):2973-83
15574598
Chromosoma. 1996 Apr;104(7):519-27
8625740
Development. 2008 Feb;135(4):699-705
18199578
J Biol Chem. 2008 Nov 21;283(47):32741-50
18819909
Cell. 2001 May 18;105(4):433-43
11371341
EMBO J. 1997 Sep 1;16(17):5280-8
9311988
EMBO J. 1994 Aug 15;13(16):3822-31
7915232
Nature. 2000 Aug 10;406(6796):593-9
10949293
Curr Biol. 2003 Dec 2;13(23):R895-8
14654010
Cell. 1994 Jul 1;77(7):993-1002
8020105
Cell. 1999 Aug 20;98(4):513-22
10481915
Proc Natl Acad Sci U S A. 1990 Dec;87(24):9923-7
2124708
J Neurobiol. 2005 Aug;64(2):157-69
15818553
Genetics. 2003 Nov;165(3):1341-54
14668387
Genetics. 2002 Jul;161(3):1125-36
12136016
Development. 2006 Jan;133(2):229-35
16339185