The Mi-2 protein is the central component of the recently isolated NuRD nucleosome remodelling and histone deacetylase complex. Although the NuRD complex has been the subject of extensive biochemical analyses, little is known about its biological function. Here we show that the two C. elegans Mi-2 homologues, LET-418 and CHD-3, play essential roles during development. The two proteins possess both shared and unique functions during vulval cell fate determination, including antagonism of the Ras signalling pathway required for vulval cell fate induction and the proper execution of the 2 degrees cell fate of vulval precursor cells, a process under the control of LIN-12 Notch signalling.
REFERENCES
Ahringer
J.
(2000
) NuRD and SIN3 histone deacetylase complexes in development.
Trends Genet
16
, 351
–356
Ambros
V.
(1999
) Cell cycle-dependent sequencing of cell fate decisions in Caenorhabditis elegans vulva precursor cells.
Development
126
, 1947
–1956
Brenner
S.
(1974
) The genetics of Caenorhabditis elegans.
Genetics
77
, 71
–94
Burdine
R. D.
, Branda
C. S.
, Stern
M. J.
(1998
) EGL-17(FGF) expression coordinates the attraction of the migrating sex myoblasts with vulval induction in C. elegans.
Development
125
, 1083
–1093
Delmas
V.
, Stokes
D. G.
, Perry
R. P.
(1993
) A mammalian DNA-binding protein that contains a chromodomain and an SNF2/ SWI2-like helicase domain.
Proc. Natl. Acad. Sci.USA
90
, 2414
–2418
Eshed
Y.
, Baum
S. F.
, Bowman
J. L.
(1999
) Distinct mechanisms promote polarity establishment in carpels of Arabidopsis.
Cell
15
, 199
–209
Ferguson
E. L.
, Sternberg
P. W.
, Horvitz
H. R.
(1987
) A genetic pathway for the specification of the vulval cell lineages of Caenorhabditis elegans.
Nature
326
, 259
–267
Ferguson
E. L.
, Horvitz
H. R.
(1989
) The multivulva phenotype of certain Caenorhabditis elegans mutants results from defects in two functionally redundant pathways.
Genetics
123
, 109
–121
Fire
A.
, Xu
S.
, Montgomery
M. K.
, Kostas
S. A.
, Driver
S. E.
, Mello
C. C.
(1998
) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.
Nature
391
, 806
–811
Greenwald
I. S.
, Sternberg
P. W.
, Horvitz
H. R.
(1983
) The lin-12 locus specifies cell fates in Caenorhabditis elegans.
Cell
34
, 435
–444
Huang
L. S.
, Tzou
P.
, Sternberg
P. W.
(1994
) The lin-15 locus encodes two negative regulators of Caenorhabditis elegans vulval development.
Mol. Biol. Cell
5
, 395
–411
Johnsen
R. C.
, Baillie
D. L.
(1991
) Genetic analysis of a major segment [LGV(left)] of the genome of Caenorhabditis elegans.
Genetics
129
, 735
–752
Kehle
J.
, Beuchle
D.
, Treuheit
S.
, Christen
B.
, Kennison
J. A.
, Bienz
M.
, Muller.
J.
(1998
) dMi-2, a hunchback-interacting protein that functions in polycomb repression.
Science
282
, 1897
–1900
Koga
M.
, Ohshima
Y.
(1995
) Mosaic analysis of the let-23 gene function in vulval induction of Caenorhabditis elegans.
Development
121
, 2655
–2666
Kornfeld
K.
(1997
) Vulval development in Caenorhabditis elegans.
Trends Genet
13
, 55
–61
Lu
X.
, Horvitz
H. R.
(1998
) lin-35 and lin-53, two genes that antagonize a C. elegans Ras pathway, encode proteins similar to Rb and its binding protein RbAp48.
Cell
95
, 981
–991
Maduro
M.
, Pilgrim
D.
(1995
) Identification and cloning of unc-119, a gene expressed in the Caenorhabditis elegans nervous system.
Genetics
141
, 977
–988
Montgomery
M. K.
, Xu
S.
, Fire
A.
(1998
) RNA as a target of double-stranded RNA-mediated genetic interference in Caenorhabditis elegans.
Proc. Natl. Acad. Sci. USA
95
, 15502
–15507
Seelig
H. P.
, Moosbrugger
I.
, Ehrfeld
H.
, Fink
T.
, Renz
M.
, Genth
E.
(1995
) The major dermatomyositis-specific Mi-2 autoantigen is a presumed helicase involved in transcriptional activation.
Arthritis Rheum
38
, 1389
–1399
Seydoux
G.
, Savage
C.
, Greenwald
I.
(1993
) Isolation and characterization of mutations causing abnormal eversion of the vulva in Caenorhabditis elegans.
Dev. Biol
157
, 423
–436
Simske
J. S.
, Kim
S. K.
(1995
) Sequential signalling during Caenorhabditis elegans vulval induction.
Nature
375
, 142
–146
Solari
F.
, Ahringer
J.
(2000
) NURD-complex genes antagonise Ras-induced vulval development in Caenorhabditis elegans.
Curr. Biol
10
, 223
–226
Sternberg
P. W.
, Horvitz
H. R.
(1986
) Pattern formation during vulval development in C. elegans.
Cell
44
, 761
–772
Sternberg
P. W.
, Horvitz
H. R.
(1989
) The combined action of two intercellular signaling pathways specifies three cell fates during vulval induction in C. elegans.
Cell
58
, 679
–693
Sternberg
P. W.
, Han
M.
(1998
) Genetics of RAS signaling in C. elegans.
Trends Genet
14
, 466
–472
Tabara
H.
, Grishok
A.
, Mello
C. C.
(1998
) RNAi in C. elegans: soaking in the genome sequence.
Science
282
, 430
–431
Thomas
J. H.
, Horvitz
H. R.
(1999
) The C. elegans gene lin-36 acts cell autonomously in the lin-35 Rb pathway.
Development
126
, 3449
–3459
Tong
J. K.
, Hassig
C. A.
, Schnitzler
G. R.
, Kingston
R. E.
, Schreiber
S. L.
(1998
) Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex.
Nature
395
, 917
–921
Wade
P. A.
, Jones
P. L.
, Vermaak
D.
, Wolffe
A. P.
(1998
) A multiple subunit Mi-2 histone deacetylase from Xenopus laevis cofractionates with an associated Snf2 superfamily ATPase.
Curr. Biol
8
, 843
–846
Wade
P. A.
, Gegonne
A.
, Jones
P. L.
, Ballestar
E.
, Aubry
F.
, Wolffe
A. P.
(1999
) Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation.
Nat. Genet
23
, 62
–66
Walhout
A. J.
, Sordella
R.
, Lu
X.
, Hartley
J. L.
, Temple
G. F.
, Brasch
M. A.
, Thierry-Mieg
N.
, Vidal
M.
(2000
) Protein interaction mapping in C. elegans using proteins involved in vulval development.
Science
287
, 116
–122
Woodage
T.
, Basrai
M. A.
, Baxevanis
A. D.
, Hieter
P.
, Collins
F. S.
(1997
) Characterization of the CHD family of proteins.
Proc. Natl. Acad. Sci. USA
94
, 11472
–11477
Xue
Y.
, Wong
J.
, Moreno
G. T.
, Young
M. K.
, Cote
J.
, Wang
W.
(1998
) NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities.
Mol. Cell
2
, 851
–861
Zhang
Y.
, LeRoy
G.
, Seelig
H. P.
, Lane
W. S.
, Reinberg
D.
(1998
) The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities.
Cell
95
, 279
–289
Zhang
Y.
, Ng
H. H.
, Erdjument-Bromage
H.
, Tempst
P.
, Bird
A.
, Reinberg
D.
(1999
) Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation.
Genes Dev
13
, 1924
–1935
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2000