Genome-wide association study follow-up identifies cyclin A2 as a regulator of the transition through cytokinesis during terminal erythropoiesis.

Am J Hematol
Authors
Keywords
Abstract

Genome-wide association studies (GWAS) hold tremendous promise to improve our understanding of human biology. Recent GWAS have revealed over 75 loci associated with erythroid traits, including the 4q27 locus that is associated with red blood cell size (mean corpuscular volume). The close linkage disequilibrium block at this locus harbors the CCNA2 gene that encodes cyclin A2. CCNA2 mRNA is highly expressed in human and murine erythroid progenitor cells and regulated by the essential erythroid transcription factor GATA1. To understand the role of cyclin A2 in erythropoiesis, we have reduced expression of this gene using short hairpin RNAs in a primary murine erythroid culture system. We demonstrate that cyclin A2 levels affect erythroid cell size by regulating the passage through cytokinesis during the final cell division of terminal erythropoiesis. Our study provides new insight into cell cycle regulation during terminal erythropoiesis and more generally illustrates the value of functional GWAS follow-up to gain mechanistic insight into hematopoiesis.

Year of Publication
2015
Journal
Am J Hematol
Volume
90
Issue
5
Pages
386-91
Date Published
2015 May
ISSN
1096-8652
URL
DOI
10.1002/ajh.23952
PubMed ID
25615569
PubMed Central ID
PMC4409486
Links
Grant list
P01 HL032262 / HL / NHLBI NIH HHS / United States
R01 DK068348 / DK / NIDDK NIH HHS / United States
R01 DK103794 / DK / NIDDK NIH HHS / United States
R21 HL120791 / HL / NHLBI NIH HHS / United States