The Human Transcription Factors.

Samuel A Lambert, Arttu Jolma, Laura F Campitelli, Pratyush K Das, Yimeng Yin, Mihai Albu, Xiaoting Chen, Jussi Taipale, Timothy R Hughes, Matthew T Weirauch

Journal: Cell 2019;172(4):650-665

PMID: 29425488

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Abstract

Transcription factors (TFs) recognize specific DNA sequences to control chromatin and transcription, forming a complex system that guides expression of the genome. Despite keen interest in understanding how TFs control gene expression, it remains challenging to determine how the precise genomic binding sites of TFs are specified and how TF binding ultimately relates to regulation of transcription. This review considers how TFs are identified and functionally characterized, principally through the lens of a catalog of over 1,600 likely human TFs and binding motifs for two-thirds of them. Major classes of human TFs differ markedly in their evolutionary trajectories and expression patterns, underscoring distinct functions. TFs likewise underlie many different aspects of human physiology, disease, and variation, highlighting the importance of continued effort to understand TF-mediated gene regulation.

Address: Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.; Donnelly Centre, University of Toronto, Toronto, ON, Canada.; Genome-Scale Biology Program, University of Helsinki, Helsinki, Finland.; Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna, Sweden.; Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.; Genome-Scale Biology Program, University of Helsinki, Helsinki, Finland; Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna, Sweden; Department of Biochemistry, Cambridge University, Cambridge CB2 1GA, United Kingdom. Electronic address: [email protected].; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Donnelly Centre, University of Toronto, Toronto, ON, Canada. Electronic address: [email protected].; Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Electronic address: [email protected].

DOI: 10.1016/j.cell.2018.01.029