Document Detail

Caenorhabditis elegans cyclin D/CDK4 and cyclin E/CDK2 induce distinct cell cycle re-entry programs in differentiated muscle cells.
MedLine Citation:
PMID:  22102824     Owner:  NLM     Status:  MEDLINE    
Cell proliferation and differentiation are regulated in a highly coordinated and inverse manner during development and tissue homeostasis. Terminal differentiation usually coincides with cell cycle exit and is thought to engage stable transcriptional repression of cell cycle genes. Here, we examine the robustness of the post-mitotic state, using Caenorhabditis elegans muscle cells as a model. We found that expression of a G1 Cyclin and CDK initiates cell cycle re-entry in muscle cells without interfering with the differentiated state. Cyclin D/CDK4 (CYD-1/CDK-4) expression was sufficient to induce DNA synthesis in muscle cells, in contrast to Cyclin E/CDK2 (CYE-1/CDK-2), which triggered mitotic events. Tissue-specific gene-expression profiling and single molecule FISH experiments revealed that Cyclin D and E kinases activate an extensive and overlapping set of cell cycle genes in muscle, yet failed to induce some key activators of G1/S progression. Surprisingly, CYD-1/CDK-4 also induced an additional set of genes primarily associated with growth and metabolism, which were not activated by CYE-1/CDK-2. Moreover, CYD-1/CDK-4 expression also down-regulated a large number of genes enriched for catabolic functions. These results highlight distinct functions for the two G1 Cyclin/CDK complexes and reveal a previously unknown activity of Cyclin D/CDK-4 in regulating metabolic gene expression. Furthermore, our data demonstrate that many cell cycle genes can still be transcriptionally induced in post-mitotic muscle cells, while maintenance of the post-mitotic state might depend on stable repression of a limited number of critical cell cycle regulators.
Jerome Korzelius; Inge The; Suzan Ruijtenberg; Martine B W Prinsen; Vincent Portegijs; Teije C Middelkoop; Marian J Groot Koerkamp; Frank C P Holstege; Mike Boxem; Sander van den Heuvel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-11-10
Journal Detail:
Title:  PLoS genetics     Volume:  7     ISSN:  1553-7404     ISO Abbreviation:  PLoS Genet.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-21     Completed Date:  2012-02-24     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101239074     Medline TA:  PLoS Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1002362     Citation Subset:  IM    
Developmental Biology, Utrecht University, Utrecht, The Netherlands.
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MeSH Terms
Animals, Genetically Modified
Caenorhabditis elegans / genetics*,  metabolism
Cell Cycle / genetics*
Cell Differentiation
Cell Proliferation
Cyclin D / genetics*,  metabolism*
Cyclin E / genetics*,  metabolism
Cyclin-Dependent Kinase 2 / genetics*,  metabolism
Cyclin-Dependent Kinase 4 / genetics*,  metabolism
DNA Replication / genetics
Gene Expression Regulation, Developmental
Muscle Cells / cytology*,  metabolism
Organ Specificity / genetics
Reg. No./Substance:
0/Cyclin D; 0/Cyclin E; EC Kinase 2; EC Kinase 4

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