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

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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Sankaran VG,Ludwig LS,Sicinska E,Xu J,Bauer DE,Eng JC,Patterson HC,Metcalf RA,Natkunam Y,Orkin SH,Sicinski P,Lander ES,Lodish HF

doi

10.1101/gad.197020.112

subject

Has Abstract

pub_date

2012-09-15 00:00:00

pages

2075-87

issue

18

eissn

0890-9369

issn

1549-5477

pii

gad.197020.112

journal_volume

26

pub_type

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