東北大学加齢医学研究所 加齢医学研究拠点 | Institute of Development, Aging and Cancer, Tohoku University

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◇平成25年12月9日(月)加齢研研究員会セミナ-のご案内
日時: 平成25年12月9日(月)15時~16時30分
場所: 加齢研SA棟 国際会議室
演題: Epigenetic Control of Chromatin-Dependent Transcription: Lessons from p53, AP-1, Brd4, and HPV
講師: Professor Cheng-Ming Chiang
所属: Simmons Comprehensive Cancer Center
Department of Pharmacology and Department of Biochemistry UT Southwestern Medical Center
担当: 井川俊太郎(所属:プロジェクト研究推進分野 ・内線8471)
要旨: Transcription in higher eukaryotes is controlled by an array of transcription factors, including the general transcription machinery, general cofactors, and gene-specific activators and repressors. The complexity of gene regulation is further conferred by the existence of multiple protein family members recognizing consensus or non-canonical DNA-binding sequences. The chromatin structure in the human genome and posttranslational modification on protein molecules provide an additional level of control in modulating gene activity. In this lecture, I will review these control mechanisms using human papillomavirus (HPV) E6 and E2 proteins as examples to illustrate how DNA tumor virus-encoded transcriptional regulators are able to reprogram cellular activities by targeting p53 tumor suppressor protein and activator protein-1 (AP-1), respectively, via recruitment of distinct coregulators, such as p300 histone acetyltransferase and the chromatin adaptor bromodomain-containing protein 4 (Brd4). The interplay among these viral and cellular proteins and the crosstalk between different posttranslational modifications regulate gene activity in response to various environmental stresses.

References:
Thomas, M.C. and C.-M. Chiang. (2005) E6 oncoprotein represses p53-dependent gene activation via inhibition of protein acetylation independently of inducing p53 degradation. Mol. Cell 17: 251-264.
Thomas, M.C. and C.-M. Chiang. (2006) The general transcription machinery and general cofactors. Critical Reviews in Biochemistry and Molecular Biology 41: 105-178.
Wu, S.-Y., A.Y. Lee, S.Y. Hou, J.K. Kemper, H. Erdjument-Bromage, P. Tempst, and C.-M. Chiang. (2006) Brd4 links chromatin targeting to HPV transcriptional silencing. Genes Dev. 20: 2383-2396.
Wu, S.-Y. and C.-M. Chiang. (2007) The double bromodomain-containing chromatin adaptor Brd4 and transcriptional regulation. J. Biol. Chem. 282: 13141-13145.
Lee, A-Y. and C.-M. Chiang. (2009) Chromatin adaptor Brd4 modulates E2 transcription activity and protein stability. J. Biol. Chem. 284: 2778-2786.
Wu, S.-Y. and C.-M. Chiang. (2009) Crosstalk between acetylation and sumoylation in regulating p53-dependent chromatin transcription and DNA binding. EMBO J. 28: 1246-1259.
Chiang, C.-M. 2009. Brd4 engagement from chromatin targeting to transcriptional regulation: selective contact with acetylated histone H3 and H4. F1000 Biology Reports 1:98.
Wang, W.-M., S.-Y. Wu, A-Y. Lee, and C.-M. Chiang. 2011. Binding site specificity and factor redundancy in activator protein-1-driven human papillomavirus chromatin-dependent transcription. J. Biol. Chem. 286: 40974-40986.
Chiang, C.-M. 2012. p53-Aurora A mitotic feedback loop regulates cell cycle progression and genomic stability. Cell Cycle 11: 3719-3720.
Wu, S.-Y., A-Y. Lee, H.-T. Lai, H. Zhang, and C.-M. Chiang. 2013. Phospho switch triggers Brd4 chromatin binding and activator recruitment for gene-specific targeting. Mol. Cell 49: 843-857.

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