Hox genes pattern the fates of the ventral ectodermal Pn.p cells that lie along the anteroposterior (A/P) body axis of C. elegans. In these cells, the Hox genes are expressed in sequential overlapping domains where they control the ability of each Pn.p cell to fuse with the surrounding syncytial epidermis. The activities of Hox proteins are sex-specific in this tissue, resulting in sex-specific patterns of cell fusion: in hermaphrodites, the mid-body cells remain unfused, whereas in males, alternating domains of syncytial and unfused cells develop. We have found that the gene egl-27, which encodes a C. elegans homologue of a chromatin regulatory factor, specifies these patterns by regulating both Hox gene expression and Hox protein function. In egl-27 mutants, the expression domains of Hox genes in these cells are shifted posteriorly, suggesting that egl-27 influences A/P positional information. In addition, egl-27 controls Hox protein function in the Pn.p cells in two ways: in hermaphrodites it inhibits MAB-5 activity, whereas in males it permits a combinatorial interaction between LIN-39 and MAB-5. Thus, by selectively modifying the activities of Hox proteins, egl-27 elaborates a simple Hox expression pattern into complex patterns of cell fates. Taken together, these results implicate egl-27 in the diversification of cell fates along the A/P axis and suggest that chromatin reorganization is necessary for controlling Hox gene expression and Hox protein function.

Reference

Ahringer
J.
(
1996
)
Posterior patterning by the Caenorhabditis eleganseven-skipped homolog vab-7.
Genes Dev
10
,
1120
1130
Ahringer
J.
(
1997
)
Maternal control of a zygotic patterning gene in Caenorhabditis elegans.
Development
124
,
3865
3869
Andrew
D. J.
,
Horner
M. A.
,
Petitt
M. G.
,
Smolik
S. M.
,
Scott
M. P.
(
1994
)
Setting limits on homeotic gene function: restraint of Sex combs reduced activity by teashirt and other homeotic genes.
EMBO J
13
,
1132
1144
Brenner
S.
(
1974
)
The genetics of C. elegans.
Genetics
77
,
71
94
Chan
S. K.
,
Jaffe
L.
,
Capovilla
M.
,
Botas
J.
,
Mann
R. S.
(
1994
)
The DNA binding specificity of Ultrabithorax is modulated by cooperative interactions with extradenticle, another homeoprotein.
Cell
78
,
603
615
Chisholm
A.
(
1991
)
Control of cell fate in the tail region of C. elegans by the gene egl-5.
Development
111
,
921
932
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
Costa
M.
,
Weir
M.
,
Coulson
A.
,
Sulston
J.
,
Kenyon
C.
(
1988
)
Posterior pattern formation in C. elegans involves position-specific expression of a gene containing a homeobox.
Cell
55
,
747
756
Cowing
D.
,
Kenyon
C.
(
1996
)
Correct Hox gene expression established independently of position in Caenorhabditis elegans.
Nature
382
,
353
356
de Zulueta
P.
,
Alexandre
E.
,
Jacq
B.
,
Kerridge
S.
(
1994
)
Homeotic complex and teashirt genes co-operate to establish trunk segmental identities in Drosophila.
Development
120
,
2287
2296
Dranginis
A. M.
(
1990
)
Binding of yeast a1 and alpha 2 as a heterodimer to the operator DNA of a haploid-specific gene.
Nature
347
,
682
685
Fasano
L.
,
Roder
L.
,
Core
N.
,
Alexandre
E.
,
Vola
C.
,
Jacq
B.
,
Kerridge
S.
(
1991
)
The gene teashirt is required for the development of Drosophila embryonic trunk segments and encodes a protein with widely spaced zinc finger motifs.
Cell
64
,
63
79
Gonzalez-Reyes
A.
,
Morata
G.
(
1990
)
The developmental effect of overexpressing a Ubx product in Drosophila embryos is dependent on its interactions with other homeotic products.
Cell
61
,
515
522
Herman
M. A.
,
Ch'ng
Q.
,
Hettenbach
S. M.
,
Ratliff
T. M.
,
Kenyon
C.
,
Herman
R. K.
(
1999
)
EGL-27 is similar to a metastasis-associated factor and controls cell polarity and cell migration in C. elegans.
Development
126
,
1055
1064
Horvitz
H. R.
,
Sternberg
P. W.
,
Greenwald
I. S.
,
Fixsen
W.
,
Ellis
H. M.
(
1983
)
Mutations that affect neural cell lineages and cell fates during the development of the nematode Caenorhabditis elegans.
Cold Spring Harb. Symp. Quant. Biol
48
,
453
463
Hunter
C. P.
,
Kenyon
C.
(
1995
)
Specification of anteroposterior cell fates in Caenorhabditis elegans by Drosophila Hox proteins.
Nature
377
,
229
232
Hunter
C. P.
,
Wood
W. B.
(
1990
)
The tra-1 gene determines sexual phenotype cell-autonomously in C. elegans.
Cell
63
,
1193
1204
Keleher
C. A.
,
Redd
M. J.
,
Schultz
J.
,
Carlson
M.
,
Johnson
A. D.
(
1992
)
Ssn6-Tup1 is a general repressor of transcription in yeast.
Cell
68
,
709
719
Kenyon
C.
(
1986
)
A gene involved in the development of the posterior body region of C. elegans.
Cell
46
,
477
487
Kenyon
C.
(
1994
)
If birds can fly, why can't we? Homeotic genes and evolution.
Cell
78
,
175
180
Kenyon
C. J.
,
Austin
J.
,
Costa
M.
,
Cowing
D. W.
,
Harris
J. M.
,
Honigberg
L.
,
Hunter
C. P.
,
Maloof
J. N.
,
Muller-Immergluck
M. M.
,
Salser
S. J.
, et al. 
(
1997
)
The dance of the Hox genes: patterning the anteroposterior body axis of Caenorhabditis elegans.
Cold Spring Harb. Symp. Quant. Biol
62
,
293
305
Kurant
E.
,
Pai
C. Y.
,
Sharf
R.
,
Halachmi
N.
,
Sun
Y. H.
,
Salzberg
A.
(
1998
)
Dorsotonals/homothorax, the Drosophila homologue of meis1, interacts with extradenticle in patterning of the embryonic PNS.
Development
125
,
1037
1048
Lin
R.
,
Hill
R. J.
,
Priess
J. R.
(
1998
)
POP-1 and anterior-posterior fate decisions in C. elegans embryos.
Cell
92
,
229
239
Lin
R.
,
Thompson
S.
,
Priess
J. R.
(
1995
)
pop-1 encodes an HMG box protein required for the specification of a mesoderm precursor in early C. elegans embryos.
Cell
83
,
599
609
Maloof
J. N.
,
Kenyon
C.
(
1998
)
The Hox gene lin-39 is required during C. elegans vulval induction to select the outcome of Ras signaling.
Development
125
,
181
190
Maloof
J. N.
,
Whangbo
J.
,
Harris
J. M.
,
Jongeward
G. D.
,
Kenyon
C.
(
1999
)
A Wnt signaling pathway controls Hox gene expression and neuroblast migration in C. elegans.
Development
126
,
37
49
Mann
R. S.
,
Abu
S. M.
(
1996
)
Nuclear import of the homeodomain protein extradenticle in response to Wg and Dpp signalling.
Nature
383
,
630
633
Mann
R. S.
,
Affolter
M.
(
1998
)
Hox proteins meet more partners.
Curr. Opin. Genet. Dev
8
,
423
429
McGinnis
N.
,
Ragnhildstveit
E.
,
Veraksa
A.
,
McGinnis
W.
(
1998
)
A cap ‘n’ collar protein isoform contains a selective Hox repressor function.
Development
125
,
4553
4564
McGinnis
W.
,
Krumlauf
R.
(
1992
)
Homeobox genes and axial patterning.
Cell
68
,
283
302
Mohler
J.
,
Mahaffey
J. W.
,
Deutsch
E.
,
Vani
K.
(
1995
)
Control of Drosophila head segment identity by the bZIP homeotic gene cnc.
Development
121
,
237
247
Pai
C. Y.
,
Kuo
T. S.
,
Jaw
T. J.
,
Kurant
E.
,
Chen
C. T.
,
Bessarab
D. A.
,
Salzberg
A.
,
Sun
Y. H.
(
1998
)
The Homothorax homeoprotein activates the nuclear localization of another homeoprotein, extradenticle, and suppresses eye development in Drosophila.
Genes Dev
12
,
435
446
Peifer
M.
,
Wieschaus
E.
(
1990
)
Mutations in the Drosophila gene extradenticle affect the way specific homeo domain proteins regulate segmental identity.
Genes Dev
4
,
1209
1223
Pinsonneault
J.
,
Florence
B.
,
Vaessin
H.
,
McGinnis
W.
(
1997
)
A model for extradenticle function as a switch that changes HOX proteins from repressors to activators.
EMBO J
16
,
2032
2042
Rauskolb
C.
,
Peifer
M.
,
Wieschaus
E.
(
1993
)
extradenticle, a regulator of homeotic gene activity, is a homolog of the homeobox-containing human proto-oncogene pbx1.
Cell
74
,
1101
1112
Rieckhof
G. E.
,
Casares
F.
,
Ryoo
H. D.
,
Abu-Shaar
M.
,
Mann
R. S.
(
1997
)
Nuclear translocation of extradenticle requires homothorax, which encodes an extradenticle-related homeodomain protein.
Cell
91
,
171
183
Ruvkun
G.
,
Holbert
O.
(
1998
)
The Taxonomy of Developmental Control in Caenorhabditis elegans.
Science
282
,
2033
2041
Salser
S. J.
,
Kenyon
C.
(
1992
)
Activation of a C. elegansAntennapedia homologue in migrating cells controls their direction of migration.
Nature
355
,
255
258
Salser
S. J.
,
Kenyon
C.
(
1996
)
A C. elegansHox gene switches on, off, on and off again to regulate proliferation, differentiation and morphogenesis.
Development
122
,
1651
1661
Salser
S. J.
,
Loer
C. M.
,
Kenyon
C.
(
1993
)
Multiple HOM-C gene interactions specify cell fates in the nematode central nervous system.
Genes Dev
7
,
1714
1724
Solari
F.
,
Bateman
A.
,
Ahringer
J.
(
1999
)
The C. elegans genes egl-27 and egr-1 are similar to MTA1, a member of a chromatin regulatory complex, and are redundantly required for embryonic patterning.
Development
126
,
2483
2494
Sulston
J. E.
,
Horvitz
H. R.
(
1977
)
Post-embryonic cell lineages of the nematode, Caenorhabditis elegans.
Dev. Biol
56
,
110
156
Toh
Y.
,
Pencil
S. D.
,
Nicolson
G. L.
(
1994
)
A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning, expression, and protein analyses.
J. Biol. Chem
269
,
22958
22963
Trent
C.
,
Tsung
N.
,
Horvitz
H. R.
(
1983
)
Egg-laying defective mutants of the nematode Caenorhabditis elegans.
Genetics
104
,
619
647
van Dijk
M. A.
,
Murre
C.
(
1994
)
extradenticle raises the DNA binding specificity of homeotic selector gene products.
Cell
78
,
617
624
Wang
B. B.
,
Muller
I. 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
Wittmann
C.
,
Bossinger
O.
,
Goldstein
B.
,
Fleischmann
M.
,
Kohler
R.
,
Brunschwig
K.
,
Tobler
H.
,
Muller
F.
(
1997
)
The expression of the C. eleganslabial -like Hox gene ceh-13 during early embryogenesis relies on cell fate and on anteroposterior cell polarity.
Development
124
,
4193
4200
Xue
D.
,
Tu
Y.
,
Chalfie
M.
(
1993
)
Cooperative interactions between the Caenorhabditis elegans homeoproteins UNC-86 and MEC-3.
Science
261
,
1324
1328
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
Zarkower
D.
,
Hodgkin
J.
(
1992
)
Molecular analysis of the C. elegans sex-determining gene tra-1: a gene encoding two zinc finger proteins.
Cell
70
,
237
249
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
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