We have molecularly characterized the lin-49 and lin-59 genes in C. elegans, and found their products are related to Drosophila trithorax group (trx-G) proteins and other proteins implicated in chromatin remodelling. LIN-49 is structurally most similar to the human bromodomain protein BR140, and LIN-59 is most similar to the Drosophila trx-G protein ASH1. In C. elegans, lin-49 and lin-59 are required for the normal development of the mating structures of the adult male tail, for the normal morphology and function of hindgut (rectum) cells in both males and hermaphrodites and for the maintenance of structural integrity in the hindgut and egg-laying system in adults. Expression of the Hox genes egl-5 and mab-5 is reduced in lin-49 and lin-59 mutants, suggesting lin-49 and lin-59 regulate HOM-C gene expression in C. elegans as the trx-G genes do in Drosophila. lin-49 and lin-59 transgenes are expressed widely throughout C. elegans animals. Thus, in contrast to the C. elegans Polycomb group (Pc-G)-related genes mes-2 and mes-6 that function primarily in the germline, we propose lin-49 and lin-59 function in somatic development similar to the Drosophila trx-G genes.
REFERENCES
Aasland
R.
, Gibson
T.
, Stewart
A. F.
(1995
) The PHD finger: implications for chromatin-mediated transcriptional regulation.
Trends Biochem. Sci
20
, 56
–59
Altschul
S. F.
, Madden
T. L.
, Schaffer
A. A.
, Zhang
J.
, Zhang
Z.
, Miller
W.
, Lipman
D. J.
(1997
) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
Nucl. Acids Res
25
, 3389
–3402
Barlev
N. A.
, Poltoratsky
V.
, Owen-Hughes
T.
, Ying
C.
, Liu
L.
, Workman
J. L.
, Berger
S. L.
(1998
) Repression of GCN5 histone acetyltransferase activity via bromodomain-mediated binding and phosphorylation by the Ku-DNA-dependent protein kinase complex.
Mol. Cell. Biol
18
, 1349
–1358
Barstead
R. J.
, Kleiman
L.
, Waterston
R. H.
(1991
) Cloning, sequencing and mapping of an alpha-actinin gene from the nematode Caenorhabditiselegans.
Cell Motil. Cytoskel
20
, 69
–78
Brizuela
B. J.
, Elfring
L.
, Ballard
J.
, Tamkun
J. W.
, Kennison
J. A.
(1994
) Genetic analysis of the brahma gene of Drosophila melanogaster and polytene chromosome subdivision 72AB.
Genetics
137
, 803
–813
Brizuela
B. J.
, Kennison
J. A.
(1997
) The Drosophila homeotic gene moira regulates expression of engrailed and HOM genes in imaginal tissues.
Mech. Dev
65
, 209
–220
sequencing consortium
(1998
) Genome sequence of the nematode C. elegans: a platform for investigating biology.
Science
282
, 2012
–2018
Candau
R.
, Zhou
J. X.
, Allis
C. D.
, Berger
S. L.
(1997
) Histone acetyltransferase activity and interaction with ADA2 are critical for GCN5 function in vivo.
EMBO J
16
, 555
–565
Capowski
E. E.
, Martin
P.
, Garvin
C.
, Strome
S.
(1991
) Identification of Grandchildless loci whose products are required for normal germ-line development in the nematode Caenorhabditiselegans.
Genetics
129
, 1061
–1072
Chamberlin
H. M.
, Palmer
R. E.
, Newman
A. P.
, Sternberg
P. W.
, Baillie
D. L.
, Thomas
J. H.
(1997
) The PAX gene egl-38 mediates developmental patterning in Caenorhabditiselegans.
Development
124
, 3919
–3928
Chamberlin
H. M.
, Brown
K. B.
, Sternberg
P. W.
, Thomas
J. H.
(1999
) Characterization of seven genes affecting Caenorhabditis elegans hindgut development.
Genetics
153
, 731
–742
Chisholm
A. D.
, Horvitz
H. R.
(1995
) Patterning of the Caenorhabditis elegans head region by the Pax-6 family member vab-3.
Nature
377
, 52
–55
Chow
K. L.
, Emmons
S. W.
(1994
) HOM-C/Hox genes and four interacting loci determine the morphogenetic properties of single cells in the nematode male tail.
Development
120
, 2579
–2593
Clark
S. G.
, Chisholm
A. D.
, Horvitz
H. R.
(1993
) Control of cell fates in the central body region of C. elegans by the homeobox gene lin-39.
Cell
74
, 43
–55
Cowing
D. W.
, Kenyon
C.
(1992
) Expression of the homeotic gene mab-5 during Caenorhabditis elegans embryogenesis.
Development
116
, 481
–490
Cui
X.
, De Vivo
I.
, Slany
R.
, Miyamoto
A.
, Firestein
R.
, Cleary
M. L.
(1998
) Association of SET domain and myotubularin-related proteins modulates growth control.
Nat. Genet
18
, 331
–337
Dhalluin
C.
, Carlson
J. E.
, Zeng
L.
, He
C.
, Aggarwal
A. K.
, Zhou
M.-M.
(1999
) Structure and ligand of a histone acetyltransferase bromodomain.
Nature
399
, 491
–496
Elfring
L. K.
, Daniel
C.
, Papoulas
O.
, Deuring
R.
, Sarte
M.
, Moseley
S.
, Beek
S. J.
, Waldrip
W. R.
, Daubresse
G.
, DePace
A.
, Kennison
J. A.
, Tamkun
J. W.
(1998
) Genetic analysis of brahma: the Drosophila homolog of the yeast chromatin remodeling factor SWI2/SNF2.
Genetics
148
, 251
–265
Fire
A.
(1986
) Integrative transformation of Caenorhabditis elegans.
EMBO J
5
, 2673
–2680
Hodgkin
J.
(1983
) Male phenotypes and mating efficiency in Caenorhabditis elegans.
Genetics
103
, 43
–64
Holdeman
R.
, Nehrt
S.
, Strome
S.
(1998
) MES-2, a maternal protein essential for viability of the germline in Caenorhabditis elegans, is homologous to a Drosophila Polycomb group protein.
Development
125
, 2457
–2467
Jeanmougin
F.
, Wurtz
J.-M.
, Le Douarin
B.
, Chambon
P.
, Losson
R.
(1997
) The bromodomain revisited.
Trends Biochem. Sci
22
, 151
–153
Kelly
W. G.
, Fire
A.
(1998
) Chromatin silencing and the maintenance of a functional germline.
Development
125
, 2451
–2456
Kennison
J. A.
(1995
) The Polycomb and trithorax group proteins of Drosophila: Trans-regulators of homeotic gene function.
Annu. Rev. Genetics
29
, 289
–303
Kenyon
C.
(1986
) A gene involved in the development of the posterior body region of C. elegans.
Cell
46
, 477
–487
Kingston
R.
, Bunker
C. A.
, Imbalzano
A. N.
(1996
) Repression and activation by multiprotein complexes that alter chromatin structure.
Genes Dev
10
, 905
–920
Korf
I.
, Fan
Y.
, Strome
S.
(1998
) The Polycomb group in Caenorhabditiselegans and maternal control of germline development.
Development
125
, 2469
–2478
Lynch
A. S.
, Briggs
D.
, Hope
I. A.
(1995
) Developmental expression pattern screen for genes predicted in the C. elegans genome sequencing project.
Nat. Genet
11
, 309
–313
Maduro
M.
, Pilgrim
D.
(1995
) Identification and cloning of unc-119, a gene expressed in the Caenorhabditis elegans nervous system.
Genetics
141
, 977
–988
Mello
C. C.
, Kramer
J. M.
, Stinchcomb
D.
, Ambros
V.
(1991
) Efficient gene transfer in C. elegans: Extrachromosomal maintenance and integration of transforming sequences.
EMBO J
10
, 3959
–3970
Papoulas
O.
, Beek
S. J.
, Moseley
S. L.
, McCallum
C. M.
, Sarte
M.
, Shearn
A.
, Tamkun
J. W.
(1998
) The Drosophila trithorax group proteins BRM, ASH1 and ASH2 are subunits of distinct protein complexes.
Development
125
, 3955
–3966
Pollard
K. J.
, Peterson
C. L.
(1998
) Chromatin remodeling: a marriage between two families?.
BioEssays
20
, 771
–780
Rozenblatt-Rosen
O.
, Rozovskaia
T.
, Burakov
D.
, Sedkov
Y.
, Tillib
S.
, Blechman
J.
, Nakamura
T.
, Croce
C. M.
, Mazo
A.
, Canaani
E.
(1998
) The C-terminal SET domains of ALL-1 and TRITHORAX interact with the INI1 and SNR1 proteins, components of the SWI/SNF complex.
Proc. Natl. Acad. Sci. USA
95
, 4152
–4157
Ruvkun
G.
, Hobert
O.
(1998
) The taxonomy of developmental control in Caenorhabditis elegans.
Science
282
, 2033
–2041
Sternberg
P. W.
, Horvitz
H. R.
(1986
) Pattern formation during vulval development in C. elegans.
Cell
14
, 761
–772
Sulston
J. E.
, Albertson
D. G.
, Thomson
J. N.
(1980
) The C. elegans male: Postembryonic development of nongonadal structures.
Dev. Biol
78
, 542
–576
Thompson
K. A.
, Wang
B.
, Argraves
W. S.
, Giancotti
F. G.
, Schranck
D. P.
, Ruoslahti
E.
(1994
) BR140, a novel zinc-finger protein with homology to the TAF250 subunit of TFIID.
Biochem. Biophys. Res. Commun
198
, 1143
–1152
Thompson
S. D.
, Higgins
D. G.
, Gibson
T. J.
(1994
) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, positions-specific gap penalties and weight matrix choice.
Nucl. Acids Res
22
, 4673
–4680
Tripoulas
N.
, Hersperger
E.
, La Jeunesse
D.
, Shearn
A.
(1994
) Molecular genetic analysis of the Drosophila melanogaster gene absent, small or homeotic discs 1 (ash1).
Genetics
137
, 1027
–1038
Tripoulas
N.
, La Jeunesse
D.
, Gildea
J.
, Shearn
A.
(1996
) The Drosophilaash1 gene product, which is localized at specific sites on polytene chromosomes, contains a SET domain and a PHD finger.
Genetics
143
, 913
–928
Wang
B. B.
, Muller-Immergluck
M. M.
, Austin
J.
, Robinson
N. T.
, Chisholm
A.
, Kenyon
C.
(1993
) A homeotic gene cluster patterns the anteroposterior body axis of C. elegans.
Cell
74
, 29
–42
Wrischnik
L. A.
, Kenyon
C. J.
(1997
) The role of lin-22, a hairy/Enhancer of split homolog, in patterning the peripheral nervous system of C. elegans.
Development
124
, 2875
–2888
This content is only available via PDF.
© 2000 by Company of Biologists
2000
-HUBSwebinar.jpg?versionId=4486)
(update)-InPreprints.png?versionId=4486)
