Genome-wide association study follow-up identifies cyclin A2 as a regulator of the transition through cytokinesis during terminal erythropoiesis
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, MCV). The close linkag...
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| Format: | Article |
| Language: | en_US |
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Wiley Blackwell
2016
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| Online Access: | http://hdl.handle.net/1721.1/105553 https://orcid.org/0000-0002-7029-7415 |
| _version_ | 1826197257915990016 |
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| author | Wakabayashi, Aoi Eng, Jennifer C. Ulirsch, Jacob C. Fleming, Mark D. Sankaran, Vijay G. Ludwig, Leif S. Cho, Hyunjii Lodish, Harvey F |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Wakabayashi, Aoi Eng, Jennifer C. Ulirsch, Jacob C. Fleming, Mark D. Sankaran, Vijay G. Ludwig, Leif S. Cho, Hyunjii Lodish, Harvey F |
| author_sort | Wakabayashi, Aoi |
| collection | MIT |
| description | 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, MCV). 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. |
| first_indexed | 2024-09-23T10:44:56Z |
| format | Article |
| id | mit-1721.1/105553 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:44:56Z |
| publishDate | 2016 |
| publisher | Wiley Blackwell |
| record_format | dspace |
| spelling | mit-1721.1/1055532022-09-27T14:43:33Z Genome-wide association study follow-up identifies cyclin A2 as a regulator of the transition through cytokinesis during terminal erythropoiesis Wakabayashi, Aoi Eng, Jennifer C. Ulirsch, Jacob C. Fleming, Mark D. Sankaran, Vijay G. Ludwig, Leif S. Cho, Hyunjii Lodish, Harvey F Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Ludwig, Leif S. Cho, Hyunjii Lodish, Harvey F 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, MCV). 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. German Academic Scholarship Foundation National Institutes of Health (U.S.) (Grant P01 HL032262) 2016-12-05T19:02:44Z 2016-12-05T19:02:44Z 2015-04 2015-01 Article http://purl.org/eprint/type/JournalArticle 03618609 1096-8652 http://hdl.handle.net/1721.1/105553 Ludwig, Leif S. et al. “Genome-Wide Association Study Follow-up Identifies Cyclin A2 as a Regulator of the Transition through Cytokinesis during Terminal Erythropoiesis: The Role of Cyclin A2 in Erythropoiesis.” American Journal of Hematology 90.5 (2015): 386–391. https://orcid.org/0000-0002-7029-7415 en_US http://dx.doi.org/10.1002/ajh.23952 American Journal of Hematology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Blackwell PMC |
| spellingShingle | Wakabayashi, Aoi Eng, Jennifer C. Ulirsch, Jacob C. Fleming, Mark D. Sankaran, Vijay G. Ludwig, Leif S. Cho, Hyunjii Lodish, Harvey F Genome-wide association study follow-up identifies cyclin A2 as a regulator of the transition through cytokinesis during terminal erythropoiesis |
| title | Genome-wide association study follow-up identifies cyclin A2 as a regulator of the transition through cytokinesis during terminal erythropoiesis |
| title_full | Genome-wide association study follow-up identifies cyclin A2 as a regulator of the transition through cytokinesis during terminal erythropoiesis |
| title_fullStr | Genome-wide association study follow-up identifies cyclin A2 as a regulator of the transition through cytokinesis during terminal erythropoiesis |
| title_full_unstemmed | Genome-wide association study follow-up identifies cyclin A2 as a regulator of the transition through cytokinesis during terminal erythropoiesis |
| title_short | Genome-wide association study follow-up identifies cyclin A2 as a regulator of the transition through cytokinesis during terminal erythropoiesis |
| title_sort | genome wide association study follow up identifies cyclin a2 as a regulator of the transition through cytokinesis during terminal erythropoiesis |
| url | http://hdl.handle.net/1721.1/105553 https://orcid.org/0000-0002-7029-7415 |
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