The suppressor of Hairy-wing [su(Hw)] gene encodes a zinc finger protein that binds to a repeated motif in the gypsy retrotransposon. These DNA sequences, called the su(Hw)-binding region, have properties of an insulator region because they (1) disrupt enhancer/silencer function in a position-dependent manner and (2) protect the mini-white gene from both euchromatic and heterochromatic position effects. To gain further insights into the types of position effects that can be insulated, we determined the effects of the su(Hw)-binding region on dosage compensation of the X-linked mini-white gene. Dosage compensation is the process that equalizes the unequal content of X-linked genes in males and females by increasing the X-linked transcription level twofold in males. Transposition of X-linked genes to the autosomes commonly results in incomplete dosage compensation, indicating that the distinct male X chromatin environment is important for this process. We found that dosage compensation of autosomally integrated mini-white genes flanked by su(Hw)-binding regions was greatly improved, such that complete or nearly complete compensation was observed at the majority of insertion sites. The su(Hw) protein was essential for this enhanced dosage compensation because in a su(Hw) mutant background compensation was incomplete. These experiments provide evidence that the su(Hw)-binding region facilitates dosage compensation of the mini-white gene on the autosomes. This may result from protection of the mini-white gene from a negative autosomal chromatin environment.

Reference

Reference
Anderson
M. G.
,
Perkins
G. L.
,
Chittick
P.
,
Shrigley
R. J.
,
Johnson
W. A.
(
1995
)
drifter, a Drosophila POU-domain transcription factor, is required for correct differentiation and migration of tracheal cells and midline glia.
Genes Dev
9
,
123
137
Baker
B. S.
,
Gorman
M.
,
Marin
I.
(
1994
)
Dosage compensation in Drosophila.
Annu. Rev. Genet
28
,
491
521
Belote
J. M.
,
Lucchesi
J. C.
(
1980
)
Male-specific lethal mutations of Drosophila melanogaster.
Genetics
96
,
165
186
Bingham
P. M.
,
Chapman
C. H.
(
1986
)
Evidence that white-blood is a novel type of temperature-sensitive mutation resulting from temperature dependent effects of a transposon insertion on formation of white transcripts.
EMBO J
5
,
3343
3351
Bingham
P. M.
,
Judd
B. H.
(
1981
)
A copy of the copia transposable element is very tightly linked to the wa allele at the white locus of D. melanogaster.
Cell
25
,
705
711
Birchler
J. A.
,
Bhadra
U.
,
Rabinow
U.
,
Linsk
U.
,
Nguyen-Huynh
A. T.
(
1994
)
Weakener of white (Wow), a gene that modifies the expression of the white eye color locus and that suppresses position effect variegation in Drosophila melanogaster.
Genetics
137
,
1057
1070
Bone
J. R.
,
Lavender
J.
,
Richman
R.
,
Palmer
M. J.
,
Turner
B. M.
,
Kuroda
M. I.
(
1994
)
Acetylated histone H4 on the male X chromosome is associated with dosage compensation in Drosophila.
Genes Dev
8
,
96
104
Chung
J. H.
,
Whiteley
M.
,
Felsenfeld
G.
(
1993
)
A 5element of the chicken b-globin domain serves as an insulator in human erythroid cells and protects against position-effect in Drosophila.
Cell
74
,
505
514
Dobzhansky
T.
(
1957
)
The X-chromosome in the larval salivary glands of hybrids Drosophila insularis × Drosophila tropicalis.
Chromosoma
8
,
691
698
Dorsett
D.
(
1993
)
Distance-independent inactivation of an enhancer by the suppressor of Hairy-wing DNA-binding protein of Drosophila.
Genetics
134
,
1135
1144
Dreesen
T. D.
,
Johnson
D. H.
,
Henikoff
S.
(
1988
)
The brown protein of Drosophila melanogaster is similar to the white protein and to components of active transport complexes.
Mol. Cell. Biol
8
,
5206
5215
Eissenberg
J. C.
,
Elgin
S. C. R.
(
1991
)
Boundary functions in the control of gene expression.
Trends in Gen
7
,
335
340
Fukunaga
A.
,
Tanaka
A.
,
Oishi
K.
(
1975
)
Maleless, a recessive autosomal mutant of Drosophila melanogaster that specifically kills male zygotes.
Genetics
81
,
135
141
Geyer
P. K.
,
Spana
C.
,
Corces
V. G.
(
1986
)
On the molecular mechanism of gypsy -induced mutations at the yellow locus of Drosophila melanogaster.
EMBO J
5
,
2657
2662
Geyer
P. K.
,
Corces
V. G.
(
1987
)
Separate regulatory elements are responsible for the complex pattern of tissue-specific and developmental transcription of the yellow locus in Drosophila melanogaster.
Genes Dev
1
,
996
1004
Geyer
P. K.
,
Green
M. M.
,
Corces
V. G.
(
1988
)
Mutant gene phenotypes mediated by a Drosophila melanogaster retrotransposon require sequences homologous to mammalian enhancers.
Proc. Natl. Acad. Sci USA
85
,
8593
8597
Geyer
P. K.
,
Corces
V. G.
(
1992
)
DNA position-specific repression of transcription by a Drosophila zinc finger protein.
Genes Dev
6
,
1865
1873
Gorman
M.
,
Kuroda
M. I.
,
Baker
B. S.
(
1993
)
Regulation of the sex-specific binding of the maleless dosage compensation protein to the male X chromosome n Drosophila.
Cell
72
,
39
49
Gorman
M.
,
Franke
A.
,
Baker
B. S.
(
1995
)
Molecular characterization of the male-specific lethal-3 gene and investigations of the regulation of dosage compensation in Drosophila.
Development
121
,
463
475
Harrison
D. A.
,
Morton
M. A.
,
Corces
V. G.
(
1992
)
The RNA polymerase II 15-kilodalton subunit is essential for viability in Drosophila melanogaster.
Mol. Cell. Biol
12
,
928
935
Harrison
D. A.
,
Gdula
D. A.
,
Coyne
R. S.
,
Corces
V. G.
(
1993
)
A leucine zipper domain of the suppressor of Hairy-wing protein mediates its repressive effect on enhancer function.
Genes Dev
7
,
1966
1978
Hazelrigg
T. R.
,
Levis
R.
,
Rubin
G. M.
(
1984
)
Transformation of white locus DNA in Drosophila: dosage compensation, zeste interaction, and position-effects.
Cell
36
,
469
481
Hilfiker
A.
,
Yang
Y.
,
Hayes
D. H.
,
Beard
C. A.
,
Manning
J. E.
,
Lucchesi
J. C.
(
1994
)
Dosage compensation in Drosophila: the X-chromosomal binding of MSL-1 and MLE is dependent on Sxl activity.
EMBO J
13
,
3542
50
Holdridge
C.
,
Dorsett
D.
(
1991
)
Repression of hsp70 heat shock gene transcription by the suppressor of Hairy-wing protein of Drosophila melanogaster.
Mol. Cell. Biol
11
,
1894
1900
Jack
J.
,
Dorsett
D.
,
Delotto
Y.
,
Liu
S.
(
1991
)
Expression of the cut locus in the Drosophila wing margin is required for cell type specification and is regulated by a distal enhancer.
Development
113
,
735
748
Kassis
J.A.
,
Noll
E.
,
Van Sickle
E.P.
,
Odenwald
W.F.
,
Perrimon
N.
(
1992
)
Altering the insertional specificity of a Drosophila transposable element.
Proc. Natl. Acad. Sci. USA
89
,
1919
1923
Kellum
R.
,
Schedl
P.
(
1991
)
A position-effect assay for boundaries of higher order chromosomal domains.
Cell
64
,
941
950
Kellum
R.
,
Schedl
P.
(
1992
)
A group of scs elements function as domain boundaries in an enhancer-blocking assay.
Mol. Cell. Biol
12
,
2424
2431
Kuroda
M. I.
,
Kernan
M. J.
,
Kreber
R.
,
Ganetzky
B.
,
Baker
B. S.
(
1991
)
The maleless protein associates with the X chromosome to regulate dosage compensation in Drosophila.
Cell
66
,
935
947
Kuroda
M. I.
,
Palmer
M. J.
,
Lucchesi
J. C.
(
1993
)
X chromosome dosage compensation in Drosophila.
Dev. Biol
4
,
107
116
Levis
R.
,
Hazelrigg
T.
,
Rubin
G. M.
(
1985
)
Effects of genomic position on the expression of transduced copies of the white gene of Drosophila.
Science
229
,
558
561
Lim
J. K.
(
1993
)
In situ hybridization with biotinylated DNA.
Drosophila Information Service
72
,
73
76
Lucchesi
J. C.
,
Skripsky
T.
,
Tax
F. E.
(
1982
)
A new male-specific lethal mutation in Drosophila melanogaster.
Genetics
100
,
42
–.
Lucchesi
J. C.
,
Manning
J. E.
(
1987
)
Gene dosage compensation in Drosophila melanogaster.
Adv. Genet
24
,
371
429
Marlor
R. L.
,
Parkhurst
S. M.
,
Corces
V. G.
(
1986
)
The Drosophila melanogastergypsy transposable element encodes putative gene products homologous to retroviral proteins.
Mol. Cell. Biol
6
,
1129
1134
Mazo
A. M.
,
Mizrokhi
L. J.
,
Karavanov
A. A.
,
Sedkov
Y. A.
,
Krichevskaja
A. A.
,
Ilyin
Y. V.
(
1989
)
Suppression in Drosophila: su(Hw) and su(f) gene products interact with a region of gypsy (mdg4) regulating its transcriptional activity.
EMBO J
8
,
903
911
Modolell
J.
,
Bender
W.
,
Meselson
M.
(
1983
)
D. melanogaster mutations suppressible by the suppressor of Hairy-wing are insertions of a 7.3 kb mobile element.
Proc. Natl. Acad. Sci. USA
80
,
1678
1682
Mukherjee
A. S.
,
Beermann
W.
(
1965
)
Synthesis of ribonucleic acid by the X-chromosomes of Drosophila melanogaster and the problem of dosage compensation.
Nature
207
,
785
786
Palmer
M.J.
,
Mergner
V. A.
,
Richman
R.
,
Manning
J. E.
,
Kuroda
M. I.
,
Lucchesi
J. C.
(
1993
)
The male-specific lethal-one (msl-1) gene of Drosophila melanogaster encodes a novel protein that associates with the X chromosome in males.
Genetics
134
,
545
557
Palmer
M.J.
,
Richman
R.
,
Richter
L.
,
Kuroda
M. I.
(
1994
)
Sex-specific regulation of the male-specific lethal-1 dosage compensation gene in Drosophila.
Genes Dev
8
,
698
706
Parkhurst
S. M.
,
Harrison
D. A.
,
Remington
M. P.
,
Spana
C.
,
Kelley
R. L.
,
Coyne
R. S.
,
Corces
V. G.
(
1988
)
The Drosophila su(Hw) gene, which controls the phenotypic effect of the gypsy transposable element, encodes a putative DNA binding protein.
Genes Dev
2
,
1205
1215
Peifer
M.
,
Bender
W.
(
1986
)
The anterobithorax and bithorax mutations of the bithorax complex.
EMBO J
9
,
2293
2303
Peifer
M.
,
Bender
W.
(
1988
)
Sequences of the gypsy transposon of Drosophila necessary for its effects on adjacent genes.
Proc. Natl. Acad. Sci. USA
85
,
9650
9654
Pirrotta
V.
,
Steller
H.
,
Bozzetti
M. P.
(
1985
)
Multiple upstream regulatory elements control the expression of the Drosophila white gene.
EMBO J
4
,
3501
3508
Qian
S.
,
Pirrotta
V.
(
1995
)
Dosage compensation of the Drosophila white gene requires both the X chromosome environment and multiple intragenic elements.
Genetics
139
,
733
744
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
Roseman
R. R.
,
Pirrotta
V.
,
Geyer
P. K.
(
1993
)
The su(Hw) protein insulates expression of the Drosophila melanogaster white gene from chromosomal position-effects.
EMBO J
12
,
435
442
Rutledge
B. J.
,
Mortin
M. A.
,
Schwarz
E.
,
Thierry-Mieg
D.
,
Meselson
M.
(
1988
)
Genetic interactions of modifier genes and modifiable alleles in D. melanogaster.
Genetics
119
,
391
397
Smith
P. A.
,
Corces
V. G.
(
1992
)
The suppressor of Hairy-wing binding region is required for gypsy mutagenesis.
Molec. Gen. Genet
233
,
65
70
Spana
C.
,
Harrison
D. A.
,
Corces
V. G.
(
1988
)
The Drosophila melanogaster suppressor of Hairy-wing protein binds to specific sequences of the gypsy retrotransposon.
Genes Dev
2
,
1414
1423
Thummel
C. S.
,
Boulet
A. M.
,
Lipschitz
H. D.
(
1988
)
Vectors for Drosophila P element-mediated transformation and tissue culture transfection.
Gene
74
,
445
456
Turner
B. M.
,
Birley
A. J.
,
Lavender
J.
(
1992
)
Histone H4 isoforms acetylated at specific lysine residues define individual chromosomes and chromatin domains in Drosophila polytene nuclei.
Cell
69
,
375
384
Uchida
S.
,
Uenoyama
T.
,
Oishi
K.
(
1981
).
Studies on the sex-specific lethals of Drosophila melanogaster. III. A third chromosome male-specific lethal mutant.
Jpn. J. Genet
56
,
523
527
Vazquez
J.
,
Schedl
P.
(
1994
)
Sequences required for enhancer blocking activity of scs are located within two nuclease-hypersensitive regions.
EMBO J
13
,
5984
5993
Wolffe
A. P.
(
1994
)
Insulating chromatin.
Current Biology
4
,
85
87
Zachar
Z.
,
Bingham
P.
(
1982
)
Regulation of white locus expression: the structure of mutant alleles of the white locus of Drosophila melanogaster.
Cell
30
,
529
541
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