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 Devjournal_title
Genes & developmentauthors
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 HFdoi
10.1101/gad.197020.112subject
Has Abstractpub_date
2012-09-15 00:00:00pages
2075-87issue
18eissn
0890-9369issn
1549-5477pii
gad.197020.112journal_volume
26pub_type
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