PT  - JOURNAL ARTICLE
AU  - Bei Wei
AU  - Arttu Jolma
AU  - Biswajyoti Sahu
AU  - Lukas M. Orre
AU  - Fan Zhong
AU  - Fangjie Zhu
AU  - Teemu Kivioja
AU  - Inderpreet Kaur Sur
AU  - Janne Lehtiö
AU  - Minna Taipale
AU  - Jussi Taipale
TI  - Strong binding activity of few transcription factors is a major determinant of open chromatin
AID  - 10.1101/204743
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 204743
4099  - http://biorxiv.org/content/early/2017/12/12/204743.short
4100  - http://biorxiv.org/content/early/2017/12/12/204743.full
AB  - It is well established that transcription factors (TFs) play crucial roles in determining cell identity, and that a large fraction of all TFs are expressed in most cell types. In order to globally characterize activities of TFs in cells, we have developed a novel massively parallel protein activity assay, Active TF Identification (ATI) that measures DNA-binding activity of all TFs from any species or tissue type. In contrast to previous studies based on mRNA expression or protein abundance, we found that a set of TFs binding to only around ten distinct motifs display strong DNA-binding activity in any given cell or tissue type. Mass spectrometric identification of TFs revealed that within these highly active TFs, there were both housekeeping TFs, which were universally found in all cell types, and specific TFs, which were highly enriched in known factors that determine the fate of the analyzed tissue or cell type. The importance of a small subset of TFs for determining the overall accessible chromatin landscape of a cell suggests that gene regulatory logic may be simpler than what has previously been appreciated.