Regulation of Arc gene transcription by SRF cofactors: mechanism and application for drug design in ASD

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460064
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: University of Toyama
• Principal Investigator: TABUCHI Akiko 富山大学, 大学院医学薬学研究部(薬学), 准教授 (40303234)
• Co-Investigator(Renkei-kenkyūsha): Mori Hisashi 富山大学, 大学院医学薬学研究部(医学), 教授 (00239617)
• Research Collaborator: FUKUCHI Mamoru 富山大学, 大学院医学薬学研究部(薬学), 助教
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 神経活動 / 血清応答因子(SRF) / MKL / Arc / 遺伝子発現 / 転写因子

Outline of Final Research Achievements

Neuronal activity controls gene expression in neurons and regulates the amounts of molecules which are involved in brain function. Activity-regulated cytoskeleton-associated protein (Arc) functions at synapses. Thus, understanding the molecular mechanism of Arc gene expression contributes to the construction of drug design for neurological disorders. Transcription factors play a central role in gene expression. One of the representative transcription factor is serum response factor (SRF). We have focused on SRF-bound cofactor, megakaryoblastic leukemia (MKL). In this study, we found that MKL2 play an important role in activating Arc gene in neurons. In addition, SOLOIST, a novel MKL2 isoform, which we discovered activated several immediate early genes. We are now generating genetically modified mice to investigate the in vivo function of SOLOIST. Furthermore, we produced MKL1 and MKL2 antibodies.

Free Research Field

分子神経生物学