東京大学医科学研究所

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学友会セミナー

学友会セミナー:2019年10月10日

開催日時: 2019年10月10日 17:00 ~ 18:00
開催場所: 総合研究棟8階 大会議室
講師: Nagai Luis Augusto Eijy
所属: 機能解析イン・シリコ分野 特任研究員
演題: 3D chromatin organizational principles involved in B-cell lymphoma gene expression
概要:

The 3D structure of the genome is complex, dynamic and plays a crucial role in controlling the transcription process of the cells. Regulation of gene expression is widely studied to understand the mechanism of transcription, and yet the fine orchestration in which genes switch on and off by distant regulatory elements remains unclear. Genome-wide chromatin conformation capture (Hi-C) became a powerful tool able to map all interactions between distant loci in the genome. Alterations of the chromatin structures are often associated with diseases. In particular, aggressive cancer development from the disruption of the humoral immune system presents abnormal gene regulation accompanied by chromatin reorganizations. In B-cell lymphomas, a hallmark is the diverse chromosomal translocations, mostly involving transcriptionally deregulation in oncogenes. For example, translocations on chromosome 7 promote constitutive activation of c-Myc genes inducing tumors in certain conditions. In this study, we focus on the chromatin dynamics in normal and abnormal B cell lymphocytes and investigate its functional impact on the regulation of oncogenes. We conducted an integrative approach using transcriptomic and epigenetic publicly available multi-omics data (Nagai et al., 2019). Although the chromatin compartments were highly preserved among several cells, 5.2% of B-cell genes in repressive compartment switched to the permissive compartment in lymphoma with increased expression levels. These genes are involved in B-cell lymphoma related biological processes, such as V(D)J recombination. We observed an inexpressive amount of significant inter-chromosomal interactions in normal cells. However, in B-cell lymphoma, 34% of the significant interactions were between distinct chromosomes. Surprisingly, about 23% of all interactions were only between chromosome 7 and 17. Such higher interaction is typical between regions in cis-chromatin interaction proximity and may indicate a translocation provoked by the "contact first" hypothesis.

世話人: 〇宮野 悟 (DNA情報解析分野)
 中井 謙太 (機能解析イン・シリコ分野)