Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number
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Lander_Cyclin D3.pdf
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1.14 MB
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Checksum (MD5)
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Author(s)
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.
Date Issued
August 2012
Journal
Genes & Development
Publisher
Cold Spring Harbor Laboratory Press
Citation
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
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Terms of Use
Creative Commons Attribution‐NonCommercial License
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DOI of Published Version
https://doi.org/10.1101/gad.197020.112
