Journal article
Genomic profiling and expression studies reveal both positive and negative activities for the Drosophila Myb MuvB/dREAM complex in proliferating cells
Genes & development, Vol.21(22), pp.2880-2896
11/15/2007
DOI: 10.1101/gad.1600107
PMCID: PMC2049191
PMID: 17978103
Abstract
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.
Details
- Title: Subtitle
- Genomic profiling and expression studies reveal both positive and negative activities for the Drosophila Myb MuvB/dREAM complex in proliferating cells
- Creators
- Daphne Georlette - Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California 94720, USASoyeon AhnDavid M MacAlpineEvelyn CheungPeter W LewisEileen L BeallStephen P BellTerry SpeedJ Robert ManakMichael R Botchan
- Resource Type
- Journal article
- Publication Details
- Genes & development, Vol.21(22), pp.2880-2896
- DOI
- 10.1101/gad.1600107
- PMID
- 17978103
- PMCID
- PMC2049191
- NLM abbreviation
- Genes Dev
- ISSN
- 0890-9369
- eISSN
- 1549-5477
- Publisher
- United States
- Grant note
- U01 HG003147 / NHGRI NIH HHS N01-CO-12400 / NCI NIH HHS R01 CA030490 / NCI NIH HHS R37 CA030490 / NCI NIH HHS N01CO12400 / NCI NIH HHS R39 CA-30490 / NCI NIH HHS
- Language
- English
- Date published
- 11/15/2007
- Academic Unit
- Stead Family Department of Pediatrics; Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9983991998902771
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