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Mammalian Transcription Factor Networks: Recent Advances in Interrogating Biological Complexity

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Wilkinson, AC 
Nakauchi, H 


Transcription factor (TF) networks are a key determinant of cell fate decisions in mammalian development and adult tissue homeostasis and are frequently corrupted in disease. However, our inability to experimentally resolve and interrogate the complexity of mammalian TF networks has hampered the progress in this field. Recent technological advances, in particular large-scale genome-wide approaches, single-cell methodologies, live-cell imaging, and genome editing, are emerging as important technologies in TF network biology. Several recent studies even suggest a need to re-evaluate established models of mammalian TF networks. Here, we provide a brief overview of current and emerging methods to define mammalian TF networks. We also discuss how these emerging technologies facilitate new ways to interrogate complex TF networks, consider the current open questions in the field, and comment on potential future directions and biomedical applications.



transcription factor regulatory network, transcription factor, transcriptional regulation, gene regulatory network, mammalian biology, stem cell biology, cancer

Journal Title

Cell Systems

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Bloodwise (15050)
Cancer Research UK (21762)
National Institute of Diabetes and Digestive and Kidney Diseases (R24DK106766)
Leukaemia & Lymphoma Research (12029)
Medical Research Council (MR/M008975/1)
Medical Research Council (MC_PC_12009)
Wellcome Trust (097922/Z/11/Z)
Wellcome Trust (105031/D/14/Z)
ACW is funded by a Bloodwise Visiting Fellowship. HN is funded by the Japan Science and Technology Agency, the California Institute of Regenerative Medicine and Ludwig Foundation. BG is funded by Bloodwise, Cancer Research UK, the Wellcome Trust, the MRC, NIH-NIDDK and core funding from the Wellcome Trust to the Cambridge Stem Cell Institute.