Transcriptional role of cyclin D1 in development revealed by a “genetic-proteomic” screen
Author manuscript: 2010 September 22.
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Nature Publishing Group
2012
|
| Online Access: | http://hdl.handle.net/1721.1/75297 https://orcid.org/0000-0001-8855-8647 |
| _version_ | 1810993221306679296 |
|---|---|
| author | Bienvenu, Frederic Jirawatnotai, Siwanon Elias, Joshua E. Meyer, Clifford A. Mizeracka, Karolina Marson, Alexander Frampton, Garrett M. Cole, Megan F. Odom, Duncan Odajima, Junko Geng, Yan Zagozdzon, Agnieszka Jecrois, Marie Young, Richard A. Liu, X. Shirley Cepko, Constance L. Gygi, Steven P. Sicinski, Piotr |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Bienvenu, Frederic Jirawatnotai, Siwanon Elias, Joshua E. Meyer, Clifford A. Mizeracka, Karolina Marson, Alexander Frampton, Garrett M. Cole, Megan F. Odom, Duncan Odajima, Junko Geng, Yan Zagozdzon, Agnieszka Jecrois, Marie Young, Richard A. Liu, X. Shirley Cepko, Constance L. Gygi, Steven P. Sicinski, Piotr |
| author_sort | Bienvenu, Frederic |
| collection | MIT |
| description | Author manuscript: 2010 September 22. |
| first_indexed | 2024-09-23T13:22:02Z |
| format | Article |
| id | mit-1721.1/75297 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:22:02Z |
| publishDate | 2012 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/752972022-10-01T14:47:24Z Transcriptional role of cyclin D1 in development revealed by a “genetic-proteomic” screen Bienvenu, Frederic Jirawatnotai, Siwanon Elias, Joshua E. Meyer, Clifford A. Mizeracka, Karolina Marson, Alexander Frampton, Garrett M. Cole, Megan F. Odom, Duncan Odajima, Junko Geng, Yan Zagozdzon, Agnieszka Jecrois, Marie Young, Richard A. Liu, X. Shirley Cepko, Constance L. Gygi, Steven P. Sicinski, Piotr Massachusetts Institute of Technology. Department of Biology Young, Richard A. Author manuscript: 2010 September 22. Cyclin D1 belongs to the core cell cycle machinery, and it is frequently overexpressed in human cancers[superscript 1, 2]. 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 retinas—an organ that critically requires cyclin D1 function[superscript 3, 4]—cyclin 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. 2012-12-07T19:28:58Z 2012-12-07T19:28:58Z 2010-01 Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/75297 Bienvenu, Frédéric et al. “Transcriptional Role of Cyclin D1 in Development Revealed by a Genetic–proteomic Screen.” Nature 463.7279 (2010): 374–378. https://orcid.org/0000-0001-8855-8647 en_US http://dx.doi.org/10.1038/nature08684 Nature Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Bienvenu, Frederic Jirawatnotai, Siwanon Elias, Joshua E. Meyer, Clifford A. Mizeracka, Karolina Marson, Alexander Frampton, Garrett M. Cole, Megan F. Odom, Duncan Odajima, Junko Geng, Yan Zagozdzon, Agnieszka Jecrois, Marie Young, Richard A. Liu, X. Shirley Cepko, Constance L. Gygi, Steven P. Sicinski, Piotr Transcriptional role of cyclin D1 in development revealed by a “genetic-proteomic” screen |
| title | Transcriptional role of cyclin D1 in development revealed by a “genetic-proteomic” screen |
| title_full | Transcriptional role of cyclin D1 in development revealed by a “genetic-proteomic” screen |
| title_fullStr | Transcriptional role of cyclin D1 in development revealed by a “genetic-proteomic” screen |
| title_full_unstemmed | Transcriptional role of cyclin D1 in development revealed by a “genetic-proteomic” screen |
| title_short | Transcriptional role of cyclin D1 in development revealed by a “genetic-proteomic” screen |
| title_sort | transcriptional role of cyclin d1 in development revealed by a genetic proteomic screen |
| url | http://hdl.handle.net/1721.1/75297 https://orcid.org/0000-0001-8855-8647 |
| work_keys_str_mv | AT bienvenufrederic transcriptionalroleofcyclind1indevelopmentrevealedbyageneticproteomicscreen AT jirawatnotaisiwanon transcriptionalroleofcyclind1indevelopmentrevealedbyageneticproteomicscreen AT eliasjoshuae transcriptionalroleofcyclind1indevelopmentrevealedbyageneticproteomicscreen AT meyerclifforda transcriptionalroleofcyclind1indevelopmentrevealedbyageneticproteomicscreen AT mizerackakarolina transcriptionalroleofcyclind1indevelopmentrevealedbyageneticproteomicscreen AT marsonalexander transcriptionalroleofcyclind1indevelopmentrevealedbyageneticproteomicscreen AT framptongarrettm transcriptionalroleofcyclind1indevelopmentrevealedbyageneticproteomicscreen AT colemeganf transcriptionalroleofcyclind1indevelopmentrevealedbyageneticproteomicscreen AT odomduncan transcriptionalroleofcyclind1indevelopmentrevealedbyageneticproteomicscreen AT odajimajunko transcriptionalroleofcyclind1indevelopmentrevealedbyageneticproteomicscreen AT gengyan transcriptionalroleofcyclind1indevelopmentrevealedbyageneticproteomicscreen AT zagozdzonagnieszka transcriptionalroleofcyclind1indevelopmentrevealedbyageneticproteomicscreen AT jecroismarie transcriptionalroleofcyclind1indevelopmentrevealedbyageneticproteomicscreen AT youngricharda transcriptionalroleofcyclind1indevelopmentrevealedbyageneticproteomicscreen AT liuxshirley transcriptionalroleofcyclind1indevelopmentrevealedbyageneticproteomicscreen AT cepkoconstancel transcriptionalroleofcyclind1indevelopmentrevealedbyageneticproteomicscreen AT gygistevenp transcriptionalroleofcyclind1indevelopmentrevealedbyageneticproteomicscreen AT sicinskipiotr transcriptionalroleofcyclind1indevelopmentrevealedbyageneticproteomicscreen |