The Sex comb on midleg (Scm) gene is a member of the Polycomb group (PcG) of genes in Drosophila melanogaster. The PcG genes encode transcriptional repressors required for proper spatial expression of homeotic genes. We report the isolation of new Scm mutations and the molecular characterization of the Scm gene. Scm mRNA is expressed maternally, at peak levels in early embryos and then at lower levels throughout the remainder of development. Scm encodes a putative zinc finger protein of 877 amino acids. Scm protein is similar to polyhomeotic, another member of the PcG, both in the zinc finger region and in a separate C-terminal domain of 60 amino acids, which we term the SPM domain. Sequence analysis of an Scm mutant allele suggests a functional requirement for the SPM domain. Scm protein also bears homology in multiple domains to a mouse protein, Rae-28 (Nomura, M., Takihara, Y. and Shimada, K. (1994) Differentiation 57,39-50) and to a fly tumor suppressor protein, the product of the lethal(3)malignant brain tumor gene (Wismar, J. et al., (1995) Mech. Dev. 53, 141–154). Possible functional relationships among these proteins and potential biochemical roles for Scm protein in PcG repression are discussed.

Reference

Reference
Adler
P. N.
,
Charlton
J.
,
Brunk
B.
(
1989
)
Genetic interactions of the Suppressor 2 of zeste region genes.
Dev. Genet
10
,
249
260
Adler
P. N.
,
Martin
E. C.
,
Charlton
J.
,
Jones
K.
(
1991
)
Phenotypic consequences and genetic interaction of a null mutation in the Drosophila Posterior Sex Combs gene.
Dev. Genet
12
,
349
361
Alkema
M. J.
,
van der Lugt
N. M. T.
,
Bobeldijk
R. C.
,
Berns
A.
,
vanLohuizen
M.
(
1995
)
Transformation of axial skeleton due to overexpression of bmi-1 in transgenic mice.
Nature
374
,
724
727
Altschul
S. F.
,
Gish
W.
,
Miller
W.
,
Myers
E. W.
,
Lipmann
D. J.
(
1990
)
Basic local alignment search tool.
J. Mol. Biol
215
,
403
410
Breen
T. R.
,
Duncan
I. M.
(
1986
)
Maternal expression of genes that regulate the bithorax complex of Drosophilamelanogaster.
Dev. Biol
118
,
442
456
Brown
N. H.
,
Kafatos
F. C.
(
1988
)
Functional cDNA libraries from Drosophila embryos.
J. Mol. Biol
203
,
425
437
Brunk
B. P.
,
Martin
E. C.
,
Adler
P. N.
(
1991
)
Drosophila genes Posterior sex combs and Suppressor two of zeste encode proteins with homology to the murine bmi-1 oncogene.
Nature
353
,
351
353
Cavener
D. R.
(
1987
)
Comparison of the consensus sequence flanking translational start sites in Drosophila and vertebrates.
Nucl. Acids Res
15
,
1353
1361
Celniker
S. E.
,
Keelan
D. J.
,
Lewis
E. B.
(
1989
)
The molecular genetics of the bithorax complex of Drosophila: characterization of the products of the Abdominal-B domain.
Genes Dev
3
,
1424
1436
Cheng
N. N.
,
Sinclair
D. A. R.
,
Campbell
R. B.
,
Brock
H. W.
(
1994
)
Interactions of polyhomeotic with Polycomb group genes of Drosophila melanogaster.
Genetics
138
,
1151
1162
Chiang
A.
,
O'Connor
M. B.
,
Paro
R.
,
Simon
J.
,
Bender
W.
(
1995
)
Discrete Polycomb-binding sites in each parasegmental domain of the bithorax complex.
Development
121
,
1681
1689
Coleman
J. E.
(
1992
)
Zinc proteins: enzymes, storage proteins, transcription factors, and replication proteins.
Annu. Rev. Biochem
61
,
897
946
DeCamillis
M.
,
Cheng
N.
,
Pierre
D.
,
Brock
H. W.
(
1992
)
The polyhomeotic gene of Drosophila encodes a chromatin protein that shares polytene chromosome-binding sites with Polycomb.
Genes Dev
6
,
223
232
Franke
A.
,
DeCamillis
M.
,
Zink
D.
,
Cheng
N.
,
Brock
H. W.
,
Paro
R.
(
1992
)
Polycomb and polyhomeotic are constitutents of a multimeric protein complex in chromatin of Drosophila melanogaster.
EMBO J
11
,
2941
2950
Gateff
E.
,
Loffler
T.
,
Wismar
J.
(
1993
)
A temperature-sensitive brain tumor suppressor mutation of Drosophila melanogaster: developmental studies and molecular localization of the gene.
Mech. Dev
41
,
15
31
Golub
T. R.
,
Barker
G. F.
,
Lovett
M.
,
Gilliland
D. G.
(
1994
)
Fusion of PDGF receptor β to a novel ets -like gene, tel, in chronic myelomonocytic leukemia with t[5;12] chromosomal translocation.
Cell
77
,
307
316
Golub
T. R.
,
Barker
G. F.
,
Bohlander
S. K.
,
Hiebert
S. W.
,
Ward
D. C.
,
Bray-Ward
P.
,
Morgan
E.
,
Raimondi
S. C.
,
Rowley
J. D.
,
Gilliland
D. G.
(
1995
)
Fusion of the tel gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia.
Proc. Natl. Acad. Sci. USA
92
,
4917
4921
Gutjahr
T.
,
Frei
E.
,
Spicer
C.
,
Baumgartner
S.
,
White
R. A. H.
,
Noll
M.
(
1995
)
The Polycomb-group gene, extra sex combs, encodes a nuclear member of the WD-40 repeat family.
EMBO J
14
,
4296
4306
Han
K.
,
Manley
J. L.
(
1993
)
Functional domains of the Drosophila Engrailed protein.
EMBO J
12
,
2723
2733
Jiang
J.
,
Ip
Y. T.
,
Kosman
D.
,
Levine
M.
(
1991
)
The dorsal morphogen gradient regulates the mesoderm determinant twist in early Drosophila embryos.
Genes Dev
5
,
1881
1891
Jones
R. S.
,
Gelbart
W. M.
(
1990
)
Genetic analysis of the Enhancer of zeste locus and its role in gene regulation in Drosophila melanogaster.
Genetics
126
,
185
199
Jones
R. S.
,
Gelbart
W. M.
(
1993
)
The Drosophila Polycomb-group gene Enhancer of zeste contains a region with sequence similarity to trithorax.
Mol. Cell. Biol
13
,
6357
6366
Jurgens
G.
(
1985
)
A group of genes controlling the spatial expression of the bithorax complex in Drosophila.
Nature
316
,
153
155
Karch
F.
,
Bender
W.
,
Weiffenbach
B.
(
1990
)
abdA expression in Drosophila embryos.
Genes Dev
4
,
1573
1587
Kaufman
T. C.
,
Lewis
R. A.
,
Wakimoto
B. T.
(
1980
)
Cytogenetic analysis of chromosome 3 in Drosophilamelanogaster: the homeotic gene complex in polytene chromosome interval 84A-B.
Genetics
94
,
115
133
Lewis
E. B.
(
1978
)
A gene complex controlling segmentation in Drosophila.
Nature
276
,
565
570
Li
M.-G.
,
McGrail
M.
,
Serr
M.
,
Hays
T. S.
(
1994
)
Drosophila cytoplasmic dynein, a microtubule motor that is asymmetrically localized in the oocyte.
J. Cell Biol
126
,
1475
1494
Lonie
A.
,
D'Andrea
R.
,
Paro
R.
,
Saint
R.
(
1994
)
Molecular characterization of the Polycomblike gene of Drosophila melanogaster, a trans-acting negative regulator of homeotic gene expression.
Development
120
,
2629
2636
Martin
E. C.
,
Adler
P. N.
(
1993
)
The Polycomb group gene Posterior sex combs encodes a chromosomal protein.
Development
117
,
641
655
Messmer
S.
,
Franke
A.
,
Paro
R.
(
1992
)
Analysis of the functional role of the Polycomb chromodomain in Drosophila melanogaster.
Genes Dev
6
,
1241
1254
Muller
J.
,
Gaunt
S.
,
Lawrence
P. A.
(
1995
)
Function of the Polycomb protein is conserved in mice and flies.
Development
121
,
2847
2852
Murre
C.
,
Bain
G.
,
van Dijk
M. A.
,
Engel
I.
,
Furnari
B. A.
,
Massari
M. E.
,
Matthews
J. R.
,
Quong
M. W.
,
Rivera
R. R.
,
Stuiver
M. H.
(
1994
)
Structure and function of helix-loop-helix proteins.
Biochim. Biophys. Acta
1218
,
129
135
Nomura
M.
,
Takihara
Y.
,
Shimada
K.
(
1994
)
Isolation and characterization of retinoic acid-inducible cDNA clones in F9 cells: one of the early inducible clones encodes a novel protein sharing several highly homologous regions with a Drosophilapolyhomeotic protein.
Differentiation
57
,
39
50
Paro
R.
,
Zink
B.
(
1992
)
The Polycomb gene is differentially regulated during oogenesis and embryogenesis of Drosophila melanogaster.
Mech. Dev
40
,
37
46
Pearce
J. J. H.
,
Singh
P. B.
,
Gaunt
S. J.
(
1992
)
The mouse has a Polycomb -like chromobox gene.
Development
114
,
921
929
Qian
S.
,
Capovilla
M.
,
Pirotta
V.
(
1993
)
Molecular mechanisms of pattern formation by the BRE enhancer of the Ubx gene.
EMBO J
12
,
3865
3877
Rastelli
L.
,
Chan
C. S.
,
Pirrotta
V.
(
1993
)
Related chromosome binding sites for zeste, suppressors of zeste and Polycomb group proteins in Drosophila and their dependence on Enhancer of zeste function.
EMBO J
12
,
1513
1522
Reijnen
M. J.
,
Hamer
K. M.
,
den Blaauwen
J. L.
,
Lambrechts
C.
,
Schoneveld
I.
,
van Driel
R.
,
Otte
A. P.
(
1995
)
Polycomb and bmi-1 homologs are expressed in overlapping patterns in Xenopus embryos and are able to interact with each other.
Mech. Dev
53
,
35
46
Robertson
H. M.
,
Preston
C. R.
,
Phillis
R. W.
,
Johnson-Schlitz
D. M.
,
Benz
W. K.
,
Engels
W. R.
(
1988
)
A stable genomic source of P element transposase in Drosophila melanogaster.
Genetics
118
,
461
470
Rost
B.
,
Sander
C.
(
1993
)
Prediction of protein secondary structure at better than 70% accuracy.
J. Mol. Biol
232
,
584
599
Rubin
G. M.
,
Spradling
A. C.
(
1982
)
Genetic transformation of Drosophila with transposable element vectors.
Science
218
,
348
353
Santamaria
P.
,
Randsholt
N. B.
(
1995
)
Characterization of a region of the X chromosome of Drosophila including multi sex combs (mxc), a Polycomb group gene which also functions as a tumour suppressor.
Mol. Gen. Genet
246
,
282
290
Sathe
S. S.
,
Harte
P. J.
(
1995
)
The Drosophilaextra sex combs protein contains WD motifs essential for its function as a repressor of homeotic genes.
Mech. Dev
52
,
77
87
Schmeichel
K. L.
,
Beckerle
M. C.
(
1994
)
The LIM domain is a modular protein-binding interface.
Cell
79
,
211
219
Seth
A.
,
Papas
T. S.
(
1990
)
The c-ets-1 proto-oncogene has oncogenic activity and is positively autoregulated.
Oncogene
5
,
1761
1767
Simon
J.
,
Chiang
A.
,
Bender
W.
(
1992
)
Ten different Polycomb group genes are required for spatial control of the abdA and AbdB homeotic products.
Development
114
,
493
505
Simon
J.
,
Bornemann
D.
,
Lunde
K.
,
Schwartz
C.
(
1995
)
The extra sex combs product contains WD40 repeats and its time of action implies a role distinct from other Polycomb group products.
Mech. Dev
53
,
197
208
Simon
J.
(
1995
)
Locking in stable states of gene expression: transcriptional control during Drosophila development.
Curr. Opin. Cell Biol
7
,
376
385
Soto
M. C.
,
Chou
T.-B.
,
Bender
W.
(
1995
)
Comparison of germline mosaics of genes in the Polycomb group of Drosophila melanogaster.
Genetics
140
,
231
243
Tamkun
J. W.
,
Deuring
R.
,
Scott
M. P.
,
Kissinger
M.
,
Pattatucci
A. M.
,
Kaufman
T. C.
,
Kennison
J. A.
(
1992
)
brahma: a regulator of Drosophila homeotic genes structurally related to the yeast transcriptional activator SNF2/SWI2.
Cell
68
,
561
572
Thummel
C. S.
,
Pirrotta
V.
(
1991
)
New pCaSpeR P element vectors.
Dros. Inf. Newslett.
2
van der Lugt
N. M. T.
,
Domen
J.
,
Linders
K.
,
Van Roon
M.
,
Robanus-Maandag
E.
,
Te Riele
H.
,
van der Valk
M.
,
Deschamps
J.
,
Sofroniew
M.
,
van Lohuizen
M.
,
Berns
A.
(
1994
).
Posterior transformations, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of the bmi-1 proto-oncogene.
Genes Dev
8
,
757
769
Wasylyk
B.
,
Hahn
S. J.
,
Giovane
A.
(
1993
)
The Ets family of transcription factors.
Eur. J. Biochem
211
,
7
18
Weintraub
S. J.
,
Prater
C. A.
,
Dean
D. C.
(
1992
)
Retinoblastoma protein switches the E2F site from positive to negative element.
Nature
358
,
259
261
White
R. A. H.
,
Wilcox
M.
(
1985
)
Distribution of Ultrabithorax proteins in Drosophila.
EMBO J
4
,
2035
2043
Wilson
C.
,
Pearson
R. K.
,
Bellen
H. J.
,
O'Kane
C. J.
,
Grossniklaus
U.
,
Gehring
W. J.
(
1989
)
P-element-mediated enhancer detection: an efficient method for isolating and characterizing developmentally regulated genes in Drosophila.
Genes Dev
3
,
1301
1313
Wismar
J.
,
Loffler
T.
,
Habtermichael
N.
,
Vef
O.
,
Geissen
M.
,
Zirwes
R.
,
Altmeyer
W.
,
Sass
H.
,
Gateff
E.
(
1995
)
The Drosophila melanogaster tumor suppressor gene lethal(3)malignant brain tumor encodes a proline-rich protein with a novel zinc finger.
Mech. Dev
53
,
141
154
Wu
C.-t.
,
Howe
M.
(
1995
)
A genetic analysis of the Suppressor 2 of zeste complex of Drosophila melanogaster.
Genetics
140
,
139
181
Zhang
C.-C.
,
Bienz
M.
(
1992
)
Segmental determination in Drosophila conferred by hunchback (hb), a repressor of the homeotic gene Ultrabithorax (Ubx).
Proc. Nat. Acad. Sci. USA
89
,
7511
7515
This content is only available via PDF.