Professor Jussi Taipale - University of Cambridge
Professor Taipale, professor of Medical Systems Biology, will present his research as part of the NCMM Seminar Series.
Jussi Taipale. Photo: University of Cambridge
Professor Jussi Taipale began his research career at the University of Helsinki, followed by postdoctoral work at Johns Hopkins University (Baltimore, MD, USA) and group leader positions at the Karolinska Institute and the University of Cambridge. His research focusses on understanding the mechanisms that control the growth of tissues and organisms, and how DNA sequence regulates when and where gene expression takes place.
Anyone interested in meeting with Professor Taipale can contact NCMM group leader Emma Haapaniemi to arrange an appointment.
Seminar title and abstract:
Genome-wide analysis of protein-DNA interactions
Understanding the information encoded in the human genome requires two genetic codes, the first code specifies how mRNA sequence is converted to protein sequence, and the second code determines where and when the mRNAs are expressed. Although the proteins that read the second, regulatory code – transcription factors (TFs) – have been largely identified, the code is poorly understood as it is not known which sequences TFs can bind in the genome. To understand the regulatory code, we have analyzed the sequence-specific binding of TFs to unmodified and epigenetically modified DNA in the presence and absence of nucleosomes, using multiple different methods. Our findings indicate that DNA commonly mediates interactions between TFs, and that dimer formation results in changes in the binding preferences of TFs. We also found that CpG methylation has both negative and positive effects on TF binding. The effect of nucleosome is largely negative, but several different TFs from diverse structural families can access nucleosomal DNA using five distinct binding modes. Despite the extensive knowledge of TF binding preferences, reading the regulatory code still remains a challenge. To address this, we have taken a multiomic approach to identify the sources of this problem by performing several experiments that bridge the gap between in vivo analyses such as massively parallel reporter assays and in vitro studies such as HT-SELEX. A binding model that is required to understand binding of TFs to the genome, which incorporates information about cellular TF DNA binding and transcriptional activity, protein-protein interactions induced by DNA, and inheritance of epigenetic states across cell division will be discussed.
The interaction landscape between transcription factors and the nucleosome.
Zhu F, Farnung L, Kaasinen E, Sahu B, Yin Y, Wei B, Dodonova SO, Nitta KR, Morgunova E, Taipale M, Cramer P, Taipale J.
Nature. 2018 Oct;562(7725):76-81. doi: 10.1038/s41586-018-0549-5. Epub 2018 Sep 24.
A protein activity assay to measure global transcription factor activity reveals determinants of chromatin accessibility.
Wei B, Jolma A, Sahu B, Orre LM, Zhong F, Zhu F, Kivioja T, Sur I, Lehtiö J, Taipale M, Taipale J.
Nat Biotechnol. 2018 Jul;36(6):521-529. doi: 10.1038/nbt.4138. Epub 2018 May 21.
Impact of cytosine methylation on DNA binding specificities of human transcription factors.
Yin Y, Morgunova E, Jolma A, Kaasinen E, Sahu B, Khund-Sayeed S, Das PK, Kivioja T, Dave K, Zhong F, Nitta KR, Taipale M, Popov A, Ginno PA, Domcke S, Yan J, Schübeler D, Vinson C, Taipale J.
Science. 2017 May 5;356(6337). pii: eaaj2239. doi: 10.1126/science.aaj2239.