Investigation of cis-elements recognized by mutatnt GATA1 by chromation immunoprecipitation sequencing analysis

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461579
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Hirosaki University
• Principal Investigator: TOKI Tsutomu 弘前大学, 医学(系)研究科(研究院), 講師 (50195731)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: GATA1 / ダウン症 / 白血病

Outline of Final Research Achievements

About 5% of Down syndrome neonates develop transient abnormal myelopoiesis (TAM). It has been reported that 20% of patients remitted develop acute megakaryoblastic leukemia. Interestingly, almost cases of the disorders harbored mutations in GATA1 gene. The mutations lead to the exclusive expression of a truncated form lacking the N-terminal domain (GATA1s). We aimed to investigate the target genes of GATA1s and to elucidate the pathogenic mechanism of TAM. We focused on three points in this project. First, identification of cis-elements and target genes of GATA1s. Second, investigation of the effect of GATA1s expression level on regulation of target gene expression. Third, probing the responsible domain for development of TAM. In this study, we reported the noble narrower region GATA1 gene for responsible to development of TAM. Next, we proved the increasing the expression of KIT gene by induction of the mutation. We also identified the cis-elements responsible for the up-regulation.

Free Research Field

血液学