Discovery of Transcription Factors and Regulatory Regions Driving Tumor Development by ATAC-seq and FAIRE-seq Open Chromatin Profiling

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The functional expression of all genes is regulated by proteins, namely transcription factors that bind to specific areas of DNA known as regulatory regions. Whereas most DNA in our genome is normally bound by other proteins (histones) and packaged into units called nucleosomes, a specific subset of tissue-specific regulatory regions is responsible for tissue-specific gene expression; these active regions are nucleosome-depleted and bound by transcription factors. We use two techniques to identify these open chromatin regions, in a normal tissue and a RasV12 induced cancer tissue. We discovered a remarkable change in the accessible regulatory landscape between these two tissues, with several thousand regions becoming more accessible in the cancer tissue. We identified two transcription factors known to be involved in cancer (AP-1 and Stat92E) controlling these newly accessible regulatory regions. Finally, we introduced a mutation resulting in Stat92E becoming non-functional in the cancer tissue, which decreased the severity of the tumor. Our study shows that open chromatin profiling can be used to identify complex in vivo processes, and we shed new light on Ras dependent cancer development.

Vyšlo v časopise: Discovery of Transcription Factors and Regulatory Regions Driving Tumor Development by ATAC-seq and FAIRE-seq Open Chromatin Profiling. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1004994
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004994

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