Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number

Vijay G. Sankaran, Leif S. Ludwig, Ewa Sicinska, Jian Xu, Daniel E. Bauer, Jennifer C. Eng, Heide Christine Patterson, Ryan A. Metcalf, Yasodha Natkunam, Stuart H. Orkin, Piotr Sicinski, Eric S. Lander, Harvey F. Lodish

Research output: Contribution to journalArticle

59 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2075-2087
Number of pages13
JournalGenes and Development
Volume26
Issue number18
DOIs
StatePublished - Sep 15 2012

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Keywords

  • Cell cycle
  • Cell division
  • Cyclin D3
  • Erythrocyte
  • Erythropoiesis
  • Genome-wide association study
  • Human genetics

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Sankaran, V. G., Ludwig, L. S., Sicinska, E., Xu, J., Bauer, D. E., Eng, J. C., Patterson, H. C., Metcalf, R. A., Natkunam, Y., Orkin, S. H., Sicinski, P., Lander, E. S., & Lodish, H. F. (2012). Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number. Genes and Development, 26(18), 2075-2087. https://doi.org/10.1101/gad.197020.112