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

Item Type:	Article
Title:	Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number
Creators Name:	Sankaran, V.G. and Ludwig, L.S. and Sicinska, E. and Xu, J. and Bauer, D.E. and Eng, J.C. and Patterson, H.C. and Metcalf, R.A. and Natkunam, Y. and Orkin, S.H. and Sicinski, P. and Lander, E.S. and Lodish, H.F.
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.
Keywords:	Cell Cycle, Cell Division, Cyclin D3, Erythrocyte, Erythropoiesis, Genome-Wide Association Study, Human Genetics, Animals, Mice
Source:	Genes & Development
ISSN:	0890-9369
Publisher:	Cold Spring Harbor Laboratory Press
Volume:	26
Number:	18
Page Range:	2075-2087
Date:	15 September 2012
Official Publication:	https://doi.org/10.1101/gad.197020.112
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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