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Genes Dev DOI:10.1101/gad.197020.112

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

Publication TypeJournal Article
Year of Publication2012
AuthorsSankaran, VG, Ludwig, LS, Sicinska, E, Xu, J, Bauer, DE, Eng, JC, Patterson, HChristine, Metcalf, RA, Natkunam, Y, Orkin, SH, Sicinski, P, Lander, ES, Lodish, HF
JournalGenes Dev
Date Published2012 Sep 15
KeywordsAnimals, Cell Count, Cell Cycle, Cell Differentiation, Cell Size, Cells, Cultured, Cyclin D3, Erythrocytes, Erythropoiesis, Gene Expression Regulation, Gene Knockdown Techniques, Humans, K562 Cells, Mice, Mice, Knockout

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.


Alternate JournalGenes Dev.
PubMed ID22929040
PubMed Central IDPMC3444733
Grant ListT32 HL007574 / HL / NHLBI NIH HHS / United States
P01 CA109901 / CA / NCI NIH HHS / United States
P01 HL032262 / HL / NHLBI NIH HHS / United States
T32 HL007574-30 / HL / NHLBI NIH HHS / United States
R01 CA108420 / CA / NCI NIH HHS / United States
P01 CA 109901 / CA / NCI NIH HHS / United States
P01 HL32262 / HL / NHLBI NIH HHS / United States
K01 DK093543 / DK / NIDDK NIH HHS / United States