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Research
The main scientific questions addressed in our laboratory relate to the understanding of molecular mechanisms that control gene regulation through the use of high-throughput biology to characterize transcription factor binding specificities and sites in human cancer cells. TFs are analyzed alone, and in combination with other TFs and scaffolding proteins such as the mediator complex. The resulting knowledge is then applied to the interpretation of large data sets such as whole cancer genomes, and genome-wide association studies that have revealed genomic regions associated with a wide variety of diseases, including heart disease, diabetes and different types of cancer. We also develop novel and better methods such as HT-SELEX, ATI, and tools for genome editing, to carry out our work in high throughput format. The work in the laboratory is interdisciplinary, and has an impact on basic scientific understanding of gene regulation, as well as to mechanisms of formation of cancer and other diseases.

The specific objectives of our research are the following:
1) To identify mechanisms that govern transcription factor binding in vitro and in live cells
2) To use the resulting information in the interpretation of cancer genomes and genome wide-association studies
3) To validate the findings in mouse genetic models

About the laboratory
Professor Jussi Taipale got his Ph.D. from the University of Helsinki in 1996, and continued with postdoctoral work at the University of Helsinki and at Johns Hopkins University (Baltimore, MD, USA). He has headed an independent research laboratory since 2003, focusing on systems biology of growth control and cancer. The main expertise of the Taipale group is high-throughput screening and computational and experimental methods to identify causative regulatory mutations in non-protein coding DNA and to analyze genetic networks. In addition, the Taipale group has extensive expertise on mouse models of gene and regulatory region function. The group is located in three countries: we are at the University of Helsinki, Finland, Karolinska Institutet, Sweden and the University of Cambridge, UK. Currently we have seven senior scientists, three postdoctoral fellows, three graduate students, three lab managers and a personal assistant.


Highlights:

Zhu et al., Nature, 2018

The packaging of DNA on nucleosomes makes it more difficult for transcription factors to access DNA. This new study shows that these proteins have evolved several different mechanisms to get around the problem, allowing them to read the important messages in our genome that tell cells how to construct and maintain our tissues and organs. The reported findings uncover a rich, interactive landscape between transcription factors... >>
Figure

Yin et al., Science, 2017

The DNA letter C exists in two forms, cytosine and methylcytosine, which can be thought of as the same letter with and without an accent (C and Ç). Methylation of DNA bases is a type of epigenetic modification, a biochemical change in the genome that doesn’t alter the DNA sequence. The two variants of C have no effect on the kind of proteins that can... >>

Jolma et al., Nature, 2015

Here, we identify TF pairs that bind cooperatively to DNA, and characterize their spacing and orientation preferences using a novel method, consecutive affinity purification SELEX (CAP-SELEX). The analysis of 9,400 potential interactions revealed 315 co-operative TF–TF pairs that recognized 618 heterodimeric motifs, most of which had not been previously described. Importantly, binding of two TFs in close proximity resulted in changes in their... >>

Jolma et al., Cell, 2013

In this work, we describe binding specificity models for the majority of all human TFs, approximately doubling the coverage compared to existing systematic studies. Our results also reveal additional specificity determinants for a large number of factors for which a partial specificity was known before, including a commonly observed A- or T-rich stretch flanking core-binding motifs. Global analysis of the data reveals that homodimer orientation... >>

Sur et al., Science, 2012

In this work, we generated mice deficient in Myc-335, a putative MYC regulatory element that contains rs6983267, a SNP accounting for more human cancer-related morbidity than any other genetic variant or mutation. In Myc-335 null mice, Myc transcripts were expressed in the intestinal crypts in a pattern similar to that in wild-type mice but at modestly reduced levels. The mutant mice displayed no overt phenotype... >>
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