Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number
Genome-wide association studies (GWASs) have identified a genetic variant of moderate effect size at 6p21.1 associated with erythrocyte traits in humans. We show that this variant affects an erythroid-specific enhancer of CCND3. A Ccnd3 knockout mouse phenocopies these erythroid phenotypes, with a d...
| Main Authors: | , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Cold Spring Harbor Laboratory Press
2014
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| Online Access: | http://hdl.handle.net/1721.1/85590 https://orcid.org/0000-0002-7029-7415 |
| _version_ | 1811090616366399488 |
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| author | Eng, Jennifer Christina Sankaran, Vijay G. Ludwig, Leif S. Sicinska, Ewa Xu, Jian Bauer, Daniel E. Patterson, Heide Christine Metcalf, Ryan A. Natkunam, Yasodha Orkin, Stuart H. Sicinski, Piotr Lander, Eric Steven Lodish, Harvey F |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Eng, Jennifer Christina Sankaran, Vijay G. Ludwig, Leif S. Sicinska, Ewa Xu, Jian Bauer, Daniel E. Patterson, Heide Christine Metcalf, Ryan A. Natkunam, Yasodha Orkin, Stuart H. Sicinski, Piotr Lander, Eric Steven Lodish, Harvey F |
| author_sort | Eng, Jennifer Christina |
| collection | MIT |
| description | Genome-wide association studies (GWASs) have identified a genetic variant of moderate effect size at 6p21.1 associated with erythrocyte traits in humans. We show that this variant affects an erythroid-specific enhancer of CCND3. A Ccnd3 knockout mouse phenocopies these erythroid phenotypes, with a dramatic increase in erythrocyte size and a concomitant decrease in erythrocyte number. By examining human and mouse primary erythroid cells, we demonstrate that the CCND3 gene product cyclin D3 regulates the number of cell divisions that erythroid precursors undergo during terminal differentiation, thereby controlling erythrocyte size and number. We illustrate how cell type-specific specialization can occur for general cell cycle components—a finding resulting from the biological follow-up of unbiased human genetic studies. |
| first_indexed | 2024-09-23T14:49:02Z |
| format | Article |
| id | mit-1721.1/85590 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:49:02Z |
| publishDate | 2014 |
| publisher | Cold Spring Harbor Laboratory Press |
| record_format | dspace |
| spelling | mit-1721.1/855902022-09-29T10:44:02Z Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number Eng, Jennifer Christina Sankaran, Vijay G. Ludwig, Leif S. Sicinska, Ewa Xu, Jian Bauer, Daniel E. Patterson, Heide Christine Metcalf, Ryan A. Natkunam, Yasodha Orkin, Stuart H. Sicinski, Piotr Lander, Eric Steven Lodish, Harvey F Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Eng, Jennifer Christina Lander, Eric S. Lodish, Harvey F. Genome-wide association studies (GWASs) have identified a genetic variant of moderate effect size at 6p21.1 associated with erythrocyte traits in humans. We show that this variant affects an erythroid-specific enhancer of CCND3. A Ccnd3 knockout mouse phenocopies these erythroid phenotypes, with a dramatic increase in erythrocyte size and a concomitant decrease in erythrocyte number. By examining human and mouse primary erythroid cells, we demonstrate that the CCND3 gene product cyclin D3 regulates the number of cell divisions that erythroid precursors undergo during terminal differentiation, thereby controlling erythrocyte size and number. We illustrate how cell type-specific specialization can occur for general cell cycle components—a finding resulting from the biological follow-up of unbiased human genetic studies. National Institutes of Health (U.S.) (Grant P01 HL32262) Amgen Inc. 2014-03-10T19:05:59Z 2014-03-10T19:05:59Z 2012-08 2012-07 Article http://purl.org/eprint/type/JournalArticle 0890-9369 1549-5477 http://hdl.handle.net/1721.1/85590 Sankaran, V. G., L. S. Ludwig, E. Sicinska, J. Xu, D. E. Bauer, J. C. Eng, H. C. Patterson, et al. “Cyclin D3 Coordinates the Cell Cycle During Differentiation to Regulate Erythrocyte Size and Number.” Genes & Development 26, no. 18 (September 15, 2012): 2075–2087. Copyright © 2012 by Cold Spring Harbor Laboratory Press https://orcid.org/0000-0002-7029-7415 en_US http://dx.doi.org/10.1101/gad.197020.112 Genes & Development Creative Commons Attribution‐NonCommercial License http://creativecommons.org/licenses/by-nc/4.0/ application/pdf Cold Spring Harbor Laboratory Press Genes and Development |
| spellingShingle | Eng, Jennifer Christina Sankaran, Vijay G. Ludwig, Leif S. Sicinska, Ewa Xu, Jian Bauer, Daniel E. Patterson, Heide Christine Metcalf, Ryan A. Natkunam, Yasodha Orkin, Stuart H. Sicinski, Piotr Lander, Eric Steven Lodish, Harvey F Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number |
| title | Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number |
| title_full | Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number |
| title_fullStr | Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number |
| title_full_unstemmed | Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number |
| title_short | Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number |
| title_sort | cyclin d3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number |
| url | http://hdl.handle.net/1721.1/85590 https://orcid.org/0000-0002-7029-7415 |
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