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在真核生物细胞核中，DNA缠绕在组蛋白上，共同组装成染色质。DNA记载了细胞各种生命活动的遗传信息，而染色质作为各种需要接触DNA的细胞过程的天然障碍，它的结构改变则提供了一种超越DNA序列本身的调控机制，即表观遗传调控。
1996年，查尔斯·戴维·阿利斯教授在Cell杂志发表文章，首次揭示组蛋白乙酰基转移酶是一类重要转录共激活物。这一突破性发现证实组蛋白能通过发生共价修饰的方式来调节基因活性，标志了表观遗传学的兴起。除乙酰化修饰外，包括甲基化、磷酸化、泛素化在内的各种组蛋白修饰以及组蛋白变体都对基因表达调控、染色质结构乃至癌症等疾病产生影响。阿利斯教授还发展了有广泛影响力的“组蛋白密码”假说，认为纷繁多样的组蛋白修饰携带了一层超越DNA序列的表观遗传信息，协同调控着基因组遗传信息的解读。
In pursuit of understanding the DNA-histone protein complex and the intricate system which allows for gene activation, the Allis lab focuses on chromatin signaling via histone modifications - acetylation, methylation and phosphorylation. Dr. Allis is best known for deciphering regulatory mechanisms that impinge upon the fundamental repeating unit of chromatin and for identifying the responsible enzyme systems that govern the covalent modifications of histone proteins, the principal components that organize chromatin. Dr. Allis discovered the critical link, through histone acetyltransferase-containing transcriptional coactivators, between targeted histone acetylation and gene-specific transcriptional activation. In further studies, he linked histone phosphorylation events to mitosis and mitogen action, established a synergy between histone phosphorylation and acetylation events and elaborated the ‘histone code hypothesis’, one of the most highly cited theories governing epigenetics. Implications of this research for human biology and human disease, notably cancer, are far-reaching and continuing at a remarkable pace.
【主讲人简介】
查尔斯·戴维·阿利斯教授是在表观遗传领域里享有崇高声誉的科学家。现为美国国家科学院、美国艺术与科学院院士，美国洛克菲勒大学染色质生物学及表观遗传学实验室主任。1996年，阿利斯教授首次证实细胞核核小体上的组蛋白不仅仅是用作染色质的骨架，组蛋白修饰还能够调节基因活性，这一突破性的发现促使了表观遗传学这一全新生命科学研究领域的诞生和兴起。
阿利斯教授为表观遗传学领域培养了诸多优秀学者，并且主编了首部表观遗传学经典教科书Epigenetics。曾获生物医学Dickson Prize（2002）、Massry奖（2003）、生物医学Wiley奖（2004）、加拿大盖尔德纳国际奖（2007）、ASBMB-Merck奖（2008）、基础医学杰出工作Lewis S. Rosenstiel Award（2011）、汤姆森路透社引文桂冠奖（2012）、日本奖（2014）、法国科学院Charles-Leopold-Meyer奖（2014）和生命科学突破奖（2015）等多项国际大奖。
Charles David Allis is currently the Joy and Jack Fishman Professor and Head of the Laboratory of Chromatin Biology and Epigenetics at The Rockefeller University. Dr. Allis is a member of the National Academy of Sciences and the American Academy of Arts and Sciences. Among his many honors are the 2014 Japan Prize, the 2011 Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Science, the 2008 ASBMB-Merck Award, the 2007 Gairdner Foundation International Award, the 2004 Wiley Prize in Biomedical Sciences, the 2003 Massry Prize and the 2002 Dickson Prize in Biomedical Sciences. |
