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Genomic profiling and expression studies reveal both positive and negative activities for the Drosophila Myb MuvB/dREAM complex in proliferating cells.

Publication ,  Journal Article
Georlette, D; Ahn, S; MacAlpine, DM; Cheung, E; Lewis, PW; Beall, EL; Bell, SP; Speed, T; Manak, JR; Botchan, MR
Published in: Genes Dev
November 15, 2007

Myb-MuvB (MMB)/dREAM is a nine-subunit complex first described in Drosophila as a repressor of transcription, dependent on E2F2 and the RBFs. Myb, an integral member of MMB, curiously plays no role in the silencing of the test genes previously analyzed. Moreover, Myb plays an activating role in DNA replication in Drosophila egg chamber follicle cells. The essential functions for Myb are executed as part of MMB. This duality of function lead to the hypothesis that MMB, which contains both known activator and repressor proteins, might function as part of a switching mechanism that is dependent on DNA sites and developmental context. Here, we used proliferating Drosophila Kc tissue culture cells to explore both the network of genes regulated by MMB (employing RNA interference and microarray expression analysis) and the genomic locations of MMB following chromatin immunoprecipitation (ChIP) and tiling array analysis. MMB occupied 3538 chromosomal sites and was promoter-proximal to 32% of Drosophila genes. MMB contains multiple DNA-binding factors, and the data highlighted the combinatorial way by which the complex was targeted and utilized for regulation. Interestingly, only a subset of chromatin-bound complexes repressed genes normally expressed in a wide range of developmental pathways. At many of these sites, E2F2 was critical for repression, whereas at other nonoverlapping sites, Myb was critical for repression. We also found sites where MMB was a positive regulator of transcript levels that included genes required for mitotic functions (G2/M), which may explain some of the chromosome instability phenotypes attributed to loss of Myb function in myb mutants.

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Published In

Genes Dev

DOI

ISSN

0890-9369

Publication Date

November 15, 2007

Volume

21

Issue

22

Start / End Page

2880 / 2896

Location

United States

Related Subject Headings

  • RNA Interference
  • Proto-Oncogene Proteins c-myb
  • Oligonucleotide Array Sequence Analysis
  • Models, Biological
  • Genome, Insect
  • Gene Expression Profiling
  • Gene Expression
  • Drosophila Proteins
  • Drosophila
  • Developmental Biology
 

Citation

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Georlette, D., Ahn, S., MacAlpine, D. M., Cheung, E., Lewis, P. W., Beall, E. L., … Botchan, M. R. (2007). Genomic profiling and expression studies reveal both positive and negative activities for the Drosophila Myb MuvB/dREAM complex in proliferating cells. Genes Dev, 21(22), 2880–2896. https://doi.org/10.1101/gad.1600107
Georlette, Daphne, Soyeon Ahn, David M. MacAlpine, Evelyn Cheung, Peter W. Lewis, Eileen L. Beall, Stephen P. Bell, Terry Speed, J Robert Manak, and Michael R. Botchan. “Genomic profiling and expression studies reveal both positive and negative activities for the Drosophila Myb MuvB/dREAM complex in proliferating cells.Genes Dev 21, no. 22 (November 15, 2007): 2880–96. https://doi.org/10.1101/gad.1600107.
Georlette D, Ahn S, MacAlpine DM, Cheung E, Lewis PW, Beall EL, et al. Genomic profiling and expression studies reveal both positive and negative activities for the Drosophila Myb MuvB/dREAM complex in proliferating cells. Genes Dev. 2007 Nov 15;21(22):2880–96.
Georlette, Daphne, et al. “Genomic profiling and expression studies reveal both positive and negative activities for the Drosophila Myb MuvB/dREAM complex in proliferating cells.Genes Dev, vol. 21, no. 22, Nov. 2007, pp. 2880–96. Pubmed, doi:10.1101/gad.1600107.
Georlette D, Ahn S, MacAlpine DM, Cheung E, Lewis PW, Beall EL, Bell SP, Speed T, Manak JR, Botchan MR. Genomic profiling and expression studies reveal both positive and negative activities for the Drosophila Myb MuvB/dREAM complex in proliferating cells. Genes Dev. 2007 Nov 15;21(22):2880–2896.

Published In

Genes Dev

DOI

ISSN

0890-9369

Publication Date

November 15, 2007

Volume

21

Issue

22

Start / End Page

2880 / 2896

Location

United States

Related Subject Headings

  • RNA Interference
  • Proto-Oncogene Proteins c-myb
  • Oligonucleotide Array Sequence Analysis
  • Models, Biological
  • Genome, Insect
  • Gene Expression Profiling
  • Gene Expression
  • Drosophila Proteins
  • Drosophila
  • Developmental Biology