染色质与表观遗传学系列讲座第18场

发布日期：2021-11-22　　浏览次数：13119

北京时间2021年11月23日（周二） 20:00-21:00

2021 November 23rd Tuesday 20:00-21:00 (Beijing Time)

Zoom网络研讨会: 843 6931 3262

Bilibili直播：http://live.bilibili.com/22741871

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Webinar ID: 843 6931 3262

Bilibili Live: http://live.bilibili.com/22741871

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主讲人 | Speaker

Adrian Bird

主讲人简介 | Speaker Biography

Dr. Adrian Bird holds the Buchanan Chair of Genetics at Edinburgh University. After obtaining his PhD at Edinburgh University and postdoctoral experience at Yale and Zurich he joined an MRC Unit in Edinburgh and later moved to Vienna, returning to Edinburgh in 1990. His research focuses on DNA methylation and other epigenetic processes, including the molecular mechanisms underlying neurological disorders.

Adrian Bird教授是英国爱丁堡大学的布坎南遗传学讲座教授。他于1971年在爱丁堡大学获得博士学位，之后在耶鲁大学和苏黎世从事博士后工作。1975年，他回到爱丁堡，加入英国医学研究委员会哺乳类基因组研究小组。1987年他成为维也纳分子病理学研究所的高级科学家，并于1990年返回爱丁堡大学任教。他的研究重点是DNA甲基化和其他表观遗传学过程，包括神经系统障碍的分子机制。他的团队率先发现了CpG岛以及MeCP2蛋白，随后延伸至DNA甲基化与蕾特氏症的关联。

报告标题 | Title

Proteins that interpret genomic signals to stabilize cell identity

The identity of differentiated cell types is remarkably stable. This lecture will explore two ways in which this is achieved via proteins that interpret genomic signals to stabilize and optimize gene expression programs. Evidence will be presented that the chromatin protein MeCP2 interprets the local DNA methylation density to modulate gene expression levels in the mature brain. Loss of MeCP2 by mutation compromises neuronal function, leading to the neurological disorder Rett syndrome. A second signal that affects gene activity globally is DNA base composition. We found that the stem cell protein SALL4, which stabilizes the embryonic stem cell state, depends for its function on binding to short AT-rich DNA sequence motifs whose frequency fluctuates dependent on base composition. Loss of this protein as cells differentiate may facilitate the differentiation process by allowing up-regulation of differentiation genes.

主讲人近年发表论文| Recent Publications

1) Lyst, M. J., R. Ekiert, J. Guy, J. Selfridge, M. V. Koerner, C. Merusi, D. De Sousa and A. Bird (2018). Affinity for DNA contributes to NLS Independent Nuclear Localization of MeCP2. Cell Rep 24(9): 2213-2220.

2) Antequera, F and A. Bird (2018). CpG Islands:  A Historical Perspective.  Methods Mol Biol 1766: 3-13.

3) Tillotson, R., J. Selfridge, M. V. Koerner, K. K. E. Gadalla, J. Guy, D. De Sousa, R. D. Hector, S. R. Cobb and A. Bird (2017). Radically truncated MeCP2 rescues Rett syndrome-like neurological defects. Nature 550(7676): 398-401.

4) Bird, A. (2017). Genetic determinants of the epigenome in development and cancer. Swiss Med Wkly 147: w14523.

5) Shah, R. R. and A. P. Bird (2017). MeCP2 mutations: progress towards understanding and treating Rett syndrome. Genome Med 9(1): 17.

6) Lagger, S., J. C. Connelly, G. Schweikert, S. Webb, J. Selfridge, B. H. Ramsahoye, M. Yu, C. He, G. Sanguinetti, L. C. Sowers, M. D. Walkinshaw and A. Bird (2017). MeCP2 recognizes cytosine methylated tri-nucleotide and di-nucleotide sequences to tune transcription in the mammalian brain. PLoS Genet 13(5): e1006793.

7) Kruusvee, V., M. J. Lyst, C. Taylor, Z. Tarnauskaite, A. P. Bird and A. G. Cook (2017). Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders. Proc Natl Acad Sci U S A 114(16): E3243-E3250.

8) Shah, R. R., J. Cholewa-Waclaw, F. C. Davies, K. M. Paton, R. Chaligne, E. Heard, C. M. Abbott and A. P. Bird (2016). Efficient and versatile CRISPR engineering of human neurons in culture to model neurological disorders. Wellcome Open Res 1: 13.

9) Quante, T. and A. Bird (2016). Do short, frequent DNA sequence motifs mould the epigenome? Nat Rev Mol Cell Biol 17(4): 257-262.

10) Ross, P. D., J. Guy, J. Selfridge, B. Kamal, N. Bahey, K. E. Tanner, T. H. Gillingwater, R. A. Jones, C. M. Loughrey, C. S. McCarroll, M. E. Bailey, A. Bird and S. Cobb (2016). Exclusive expression of MeCP2 in the nervous system distinguishes between brain and peripheral Rett syndrome-like phenotypes. Hum Mol Genet 25(20): 4389-4404.

11) Lyst, M. J., J. Connelly, C. Merusi and A. Bird (2016). Sequence-specific DNA binding by AT-hook motifs in MeCP2. FEBS Lett 590(17): 2927-2933.

12) Brown, K., J. Selfridge, S. Lagger, J. Connelly, D. De Sousa, A. Kerr, S. Webb, J. Guy, C. Merusi, M. V. Koerner and A. Bird (2015). The molecular basis of variable phenotypic severity among common missense mutations causing Rett syndrome. Hum Mol Genet. 3: 558-570.

13) Cholewa-Waclaw, J., A. Bird, M. von Schimmelmann, A. Schaefer, H. Yu, H. Song, R. Madabhushi and L. H. Tsai (2016). The role of epigenetic mechanisms in the regulation of gene expression in the nervous system. J Neurosci 36(45): 11427-11434.

14) Katz, D. M., A. Bird, M. Coenraads, S. J. Gray, D. U. Menon, B. D. Philpot and D. C. Tarquinio (2016). Rett Syndrome: Crossing the Threshold to Clinical Translation. Trends Neurosci 39(2): 100-113.

15) Lyst, M. J. and A. Bird (2015). Rett syndrome: a complex disorder with simple roots. Nat Rev Genet 16(5): 261-275.

16) Cook, P. C., H. Owen, A. M. Deaton, J. G. Borger, S. L. Brown, T. Clouaire, G. R. Jones, L. H. Jones, R. J. Lundie, A. K. Marley, V. L. Morrison, A. T. Phythian-Adams, E. Wachter, L. M. Webb, T. E. Sutherland, G. D. Thomas, J. R. Grainger, J. Selfridge, A. N. McKenzie, J. E. Allen, S. C. Fagerholm, R. M. Maizels, A. C. Ivens, A. Bird and A. S. MacDonald (2015). A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells. Nat Commun 6: 6920.

17) Illingworth, R.S., Gruenewald-Schneider, U., De Sousa, D., Webb, S., Merusi, C., Kerr, A.R., James, K.D., Smith, C., Walker, R., Andrews, R., and Bird, A.P. (2015). Inter-individual variability contrasts with regional homogeneity in the human brain DNA methylome. Nucleic acids research 10.1093/nar/gku1305.

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