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The MSL complex levels are critical for its correct targeting to the chromosomes in Drosophila melanogaster

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Abstract

In Drosophila, dosage compensation requires assembly of the Male Specific Lethal (MSL) protein complex for doubling transcription of most X-linked genes in males. The recognition of the X chromosome by the MSL complex has been suggested to include initial assembly at ~35 chromatin entry sites and subsequent spreading of mature complexes in cis to numerous additional sites along the chromosome. To understand this process further we examined MSL patterns in a range of wild-type and mutant backgrounds producing different amounts of MSL components. Our data support a model in which MSL complex binding to the X is directed by a hierarchy of target sites that display different affinities for the MSL proteins. Chromatin entry sites differ in their ability to provide local intensive binding of complexes to adjacent regions, and need high MSL complex titers to achieve this. We also mapped a set of definite autosomal regions (~70) competent to associate with the functional MSL complex in wild-type males. Overexpression of both MSL1 and MSL2 stabilizes this binding and results in inappropriate MSL binding to the chromocenter and the 4th chromosome. Thus, wild-type MSL complex titers are critical for correct targeting to the X chromosome.

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Acknowledgements

We thank R.L. Kelley for the gift of transgenic and mutant strains and for critical reading of the manuscript. The help of A.A. Gorchakov in immunoblotting, and critical reading of the manuscript by S.A. Demakov and M.L. Balasov are gratefully acknowledged. This work was supported by FIRCA grant (International Cooperation Program) N1 R03-TW05669-01, grants of Russian Federation (RFBR grants) N 02-04-48222 and 00-15-97984 and the Howard Hughes Medical Institute. M.I.K. is an Investigator of the Howard Hughes Medical Institute. The experiments described here comply with the laws of the country in which the experiments were performed.

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Authors and Affiliations

  1. Institute of Cytology and Genetics, Siberian Division of Russian Academy of Sciences, 630090, Novosibirsk, Russia

    Olga V. Demakova, Irina V. Kotlikova & Igor F. Zhimulev

  2. Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA

    Polina R. Gordadze, Artyom A. Alekseyenko & Mitzi I. Kuroda

Authors
  1. Olga V. Demakova
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  2. Irina V. Kotlikova
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  3. Polina R. Gordadze
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  4. Artyom A. Alekseyenko
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  5. Mitzi I. Kuroda
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  6. Igor F. Zhimulev
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Correspondence to Igor F. Zhimulev.

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Communicated by E.R. Schmidt

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Demakova, O.V., Kotlikova, I.V., Gordadze, P.R. et al. The MSL complex levels are critical for its correct targeting to the chromosomes in Drosophila melanogaster . Chromosoma 112, 103–115 (2003). https://doi.org/10.1007/s00412-003-0249-1

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  • DOI: https://doi.org/10.1007/s00412-003-0249-1

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