报告题目：Systematic identification of silencer elements in the human genome

报告人：庞宝旭 副教授 荷兰莱顿大学医学中心

报告时间：2021年9月29日（周三）13:30

报告地点：基础楼二楼会议室

报告人简介：

2013年博士毕业于荷兰癌症研究所，2013-2014年在荷兰癌症研究所从事博士后工作，2014年至2018年，在斯坦福大学医学院遗传系从事博士后工作。2018年至2021年，在荷兰莱顿大学医学中心化学和细胞生物学系担任助理教授，2021年至今，在荷兰莱顿大学医学中心化学和细胞生物学系担任副教授。 博士工作期间，基于蒽环化疗药物，发现并定义了一种全新的药物作用机制－药物直接介导组蛋白从染色质的脱离，从而影响细胞的表观遗传学和对DNA损伤的修复。相关研究结果以第一作者或共同通讯作者发表在《Nature Communications》, 《Cancer Research 》,《Nature Chemical Biology 》等杂志。博士后工作期间研发两种高通量筛选系统对基因组非编码调节区的功能进行研究。

报告摘要：

The majority of the human genome does not encode proteins. Many of these noncoding regions contain important regulatory sequences that control gene expression. To date, most studies have focused on activators such as enhancers, but regions that repress gene expression-silencers-have not been systematically studied. We have developed a system that identifies silencer regions in a genome-wide fashion on the basis of silencer-mediated transcriptional repression of caspase 9. We found that silencers are widely distributed and may function in a tissue-specific fashion. These silencers harbor unique epigenetic signatures and are associated with specific transcription factors. Silencers also act at multiple genes, and at the level of chromosomal domains and long-range interactions. Deletion of silencer regions linked to the drug transporter genes ABCC2 and ABCG2 caused chemo-resistance. Overall, our study demonstrates that tissue-specific silencing is widespread throughout the human genome and probably contributes substantially to the regulation of gene expression and human biology.