MSL1 plays a central role in assembly of the MSL complex, essential for dosage compensation in Drosophila.
In male Drosophila, histone H4 acetylated at Lys16 is enriched on the X chromosome, and most X-linked genes are transcribed at a higher rate than in females (thus achieving dosage compensation). Five proteins, collectively called the MSLs, are required for dosage compensation and male viability. Here we show that one of these proteins, MSL1, interacts with three others, MSL2, MSL3 and MOF. The latter is a putative histone acetyl transferase. Overexpression of either the N- or C-terminal domain of MSL1 has dominant-negative effects, i.e. causes male-specific lethality. The lethality due to expression of the N-terminal domain is reduced if msl2 is co-overexpressed. MSL2 co-purifies over a FLAG affinity column with the tagged region of MSL1, and both MSL3 and MOF co-purify with the FLAG-tagged MSL1 C-terminal domain. Furthermore, the MSL1 C-terminal domain binds specifically to a GST-MOF fusion protein and co-immunoprecipitates with HA-tagged MSL3. The MSL1 C-terminal domain shows similarity to a region of mouse CBP, a transcription co-activator. We conclude that a main role of MSL1 is to serve as the backbone for assembly of the MSL complex.
Scott
M J
MJ
Institute of Molecular BioSciences, Massey University, Palmerston North, New Zealand. M.J.Scott@massey.ac.nz
Pan
L L
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Cleland
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SB
Knox
A L
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Heinrich
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D000595:Amino Acid Sequence; D000818:Animals; D002846:Chromatography, Affinity; D004396:Coloring Agents; D004268:DNA-Binding Proteins / Q000378:metabolism; D004303:Dosage Compensation, Genetic; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D007211:Indoles; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014960:X Chromosome / Q000378:metabolism; D016335:Zinc Fingers
D004396:Coloring Agents; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D007211:Indoles; D009687:Nuclear Proteins; D014157:Transcription Factors; C082132:msl-1 protein, Drosophila; C094166:msl-2 protein, Drosophila; C007293:DAPI