Identification of cardiomyocyte-specific transcriptional mechanism of c-myc

• Project/Area Number: 22890103
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Osaka University
• Principal Investigator: TSUKAMOTO Osamu 大阪大学, 医学系・研究科, 特任研究員 (80589151)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,068,000 (Direct Cost: ¥2,360,000、Indirect Cost: ¥708,000); Fiscal Year 2011: ¥1,469,000 (Direct Cost: ¥1,130,000、Indirect Cost: ¥339,000); Fiscal Year 2010: ¥1,599,000 (Direct Cost: ¥1,230,000、Indirect Cost: ¥369,000)
• Keywords: c-myc / 転写複合体 / 心筋細胞特異的遺伝子発現制御 / クロスリンク反応

Research Abstract

We found that the expression of one gene is down-regulated in cardiomyocytes while up-regulated in HUVEC or smooth muscle cells by c-myc. To clarify this cardiomyocyte-specific transcriptional mechanism by c-myc, we developed the nuclear extraction method that can obtain structurally-intact transcription complexes binding with high-affinity to their specific DNA sequences. Next, we narrowed the range of putative binding site of c-myc transcription complexes in promoter region of the gene by using both comparative genomics approach and transactivation assay. We performed DNA affinity chromatography using oligonucleotides containing the binding site of c-myc transcription complex as bait and nuclear extracts from cardiomyocytes or HUVEC. Using a high-sensitive LC-MS/ MS technology, we identified cardiomyocyte-specific components in c-myc transcription complexes.

Research Products

• [Journal Article] It is Time to Reconsider the Cardiovascular Protection Afforded by RAAS Blockade-Overview of RAAS Systems (2012)
  • Author(s): Tsukamoto O and Kitakaze M.
  • Journal Title: Cardiovasc Drugs Ther Volume: (in press)
  • Peer Reviewed
• [Journal Article] It is Time to Reconsider the Cardiovascular Protection Afforded by RAAS Blockade-Overview of RAAS Systems (2011)
  • Author(s): Osamu Tsukamoto
  • Journal Title: Cardiovascular Drugs and Therapy Volume: 27 Issue: 2 Pages: 133-138
  • DOI: 10.1007/s10557-011-6361-1
  • Peer Reviewed
• [Journal Article] Differential regulation of proteasome function in isoproterenol-induced cardiac hypertrophy (2010)
  • Author(s): Drews O, Tsukamoto O, Liem D, Streicher J, Wang Y, Ping P.
  • Journal Title: Circ Res Volume: 107 Pages: 1094-1101
  • Peer Reviewed
• [Journal Article] Isoform-specific intermolecular disulfide bond formation of heterochromatin protein 1(HP1) (2010)
  • Author(s): Higo S, Asano Y, Kato H, Yamazaki S, Nakano A, Tsukamoto O, Seguchi O, Asai M, Asakura M, Asanuma H, Sanada S, Minamino T, Komuro I, Kitakaze M, Takashima S.
  • Journal Title: J Biol Chem Volume: 285 Pages: 31337-31347
  • Peer Reviewed
• [Journal Article] Ablation of C/ EBP Homologous Protein Attenuates Endoplasmic Reticulum-Mediated Apoptosis and Cardiac Dysfunction Induced by Pressure Overload (2010)
  • Author(s): Fu HY, Okada K, Liao Y, Tsukamoto O, Isomura T, Asai M, Sawada T, Okuda K, Asano Y, Sanada S, Asanuma H, Asakura M, Takashima S, Komuro I, Kitakaze M, Minamino T.
  • Journal Title: Circulation Volume: 122 Pages: 361-369
  • Peer Reviewed
• [Journal Article] What is the role of ER stress in the heart? Introduction and series overview (2010)
  • Author(s): Kitakaze M and Tsukamoto O.
  • Journal Title: Circ Res Volume: 208 Pages: 15-18
  • Peer Reviewed
• [Journal Article] X-box binding protein 1 regulates brain natriuretic peptide through a novel AP1/ CRE-like element in cardiomyocytes (2010)
  • Author(s): Sawada T, Minamino T, Fu HY, Asai M, Okuda K, Isomura T, Yamazaki S, Asano Y, Okada K, Tsukamoto O, Sanada S, Asanuma H, Asakura M, Takashima S, Kitakaze M, Komuro I.
  • Journal Title: J Mol Cell Cardiol Volume: 48 Pages: 1280-1289
  • Peer Reviewed
• [Journal Article] Functional alterations of cardiac proteasomes under physiological and pathological conditions (2010)
  • Author(s): Tsukamoto O, Minamino T, Kitakaze M.
  • Journal Title: Cardiovasc Res Volume: 85 Pages: 339-346
  • Peer Reviewed
• [Journal Article] Differential regulation of proteasome function in isoproterenol-induced cardiac hypertrophy. (2010)
  • Author(s): Drews O, Tsukamoto O
  • Journal Title: Circulation Research Volume: 107 Pages: 1094-1101
  • Peer Reviewed
• [Journal Article] Isoform-specific intermolecular disulfide bond formation of heterochromatin protein 1. (2010)
  • Author(s): Higo S, Tsukamoto O
  • Journal Title: Journal of Biological Chemistry Volume: 285 Pages: 361-369
  • Peer Reviewed
• [Journal Article] Ablation of C/EBP homologous protein attenuates ER-mediated apoptosis and cardiac dysfunction induced by pressure overload. (2010)
  • Author(s): Fu HY, Tsukamoto O
  • Journal Title: Circulation Volume: 122 Pages: 361-369
  • Peer Reviewed
• [Journal Article] What is the role of ER stress? Introduciton and series overview. (2010)
  • Author(s): Kitakaze M, Tsukamoto O
  • Journal Title: Circulation Research Volume: 107 Pages: 15-18
  • Peer Reviewed