2012 Fiscal Year Final Research Report
Roleofrheumatoidarthritis-relatedproteinPAD4inhematopoiesis
| Project/Area Number |
23791107
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Keywords | シトルリン化 / エピジェネティクス / 造血 |
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| Research Abstract |
Peptidylarginine deiminase 4 (PAD4) functions as a transcriptional co-regulator bycatalyzing the conversion of histone H3 arginine residues to citrulline residues. Although the high level of PAD4 expression in bone marrow cells suggests itsinvolvement in hematopoiesis, its precise contribution remains unclear. Here, weshow that PAD4, which is highly expressed in lineage- Sca1+ c-kit (LSK) cells of mousebone marrow compared with other progenitor cells, controls c-myc expression bycatalyzing the citrullination of histone H3 on its promoter. Furthermore, PAD4 isassociated with lymphoid enhancer-binding factor 1 and histone deacetylase 1 at theupstream region of the c-myc gene. Supporting these findings, LSK cells, especiallymulti-potent progenitors (MPPs), in PAD4-deficient mice show increased proliferationin a cell-autonomous fashion compared with those in wild-type mice. Together, ourresults strongly suggest that PAD4 regulates the proliferation of MPPs in the bonemarrow by controlling c-myc expression.
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[Journal Article] Obesity-Associated AutoantibodyProductionRequiresAIMto Retain the Immunoglobulin M Immune ComplexonFollicularDendriticCells2013
Author(s)
SatokoArai,NatsumiMaehara,Yoshihiro Iwamura,Shin-ichiroHonda,Katsuhiko Nakashima,ToshihiroKai,MasatoOgishi, Kumiko Morita, Jun Kurokawa, Mayumi Mori, Yuji Motoi, Kensuke Miyake, NobuyukiMatsuhashi,Ken-ichiYamamura, OsamuOhara,AkiraShibuya,EdwardK. Wakeland, Quan-Zhen Li, and Toru Miyazaki
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Journal Title
Cell Rep
Volume: 3
Pages: 1-12
DOI
Peer Reviewed
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