Publication: Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen
Issued Date
2010-01-21
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ISSN
14764687
00280836
00280836
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2-s2.0-75149175161
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Mahidol University
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SCOPUS
Bibliographic Citation
Nature. Vol.463, No.7279 (2010), 374-378
Suggested Citation
Frédéric Bienvenu, Siwanon Jirawatnotai, Joshua E. Elias, Clifford A. Meyer, Karolina Mizeracka, Alexander Marson, Garrett M. Frampton, Megan F. Cole, Duncan T. Odom, Junko Odajima, Yan Geng, Agnieszka Zagozdzon, Marie Jecrois, Richard A. Young, X. Shirley Liu, Constance L. Cepko, Steven P. Gygi, Piotr Sicinski Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen. Nature. Vol.463, No.7279 (2010), 374-378. doi:10.1038/nature08684 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/29988
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Title
Transcriptional role of cyclin D1 in development revealed by a genetic-proteomic screen
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Abstract
Cyclin D1 belongs to the core cell cycle machinery, and it is frequently overexpressed in human cancers. The full repertoire of cyclin D1 functions in normal development and oncogenesis is unclear at present. Here we developed Flag-and haemagglutinin-tagged cyclin D1 knock-in mouse strains that allowed a high-throughput mass spectrometry approach to search for cyclin D1-binding proteins in different mouse organs. In addition to cell cycle partners, we observed several proteins involved in transcription. Genome-wide location analyses (chromatin immunoprecipitation coupled to DNA microarray; ChIP-chip) showed that during mouse development cyclin D1 occupies promoters of abundantly expressed genes. In particular, we found that in developing mouse retinasan organ that critically requires cyclin D1 functioncyclin D1 binds the upstream regulatory region of the Notch1 gene, where it serves to recruit CREB binding protein (CBP) histone acetyltransferase. Genetic ablation of cyclin D1 resulted in decreased CBP recruitment, decreased histone acetylation of the Notch1 promoter region, and led to decreased levels of the Notch1 transcript and protein in cyclin D1-null (Ccnd1-/-) retinas. Transduction of an activated allele of Notch1 into Ccnd1-/-retinas increased proliferation of retinal progenitor cells, indicating that upregulation of Notch1 signalling alleviates the phenotype of cyclin D1-deficiency. These studies show that in addition to its well-established cell cycle roles, cyclin D1 has an in vivo transcriptional function in mouse development. Our approach, which we term genetic-proteomic, can be used to study the in vivo function of essentially any protein. © 2010 Macmillan Publishers Limited. All rights reserved.