Multivalency regulates activity in an intrinsically disordered transcription factor
- Oregon State University, United States
- Portland State University, United States
- St. Vincent's Institute of Medical Research, Australia
- Masaryk University, Czech Republic
- University of Canterbury, New Zealand
Abstract
The transcription factor ASCIZ (ATMIN, ZNF822) has an unusually high number of recognition motifs for the product of its main target gene, the hub protein LC8 (DYNLL1). Using a combination of biophysical methods, structural analysis by NMR and electron microscopy, and cellular transcription assays, we developed a model that proposes a concerted role of intrinsic disorder and multiple LC8 binding events in regulating LC8 transcription. We demonstrate that the long intrinsically disordered C-terminal domain of ASCIZ binds LC8 to form a dynamic ensemble of complexes with a gradient of transcriptional activity that is inversely proportional to LC8 occupancy. The preference for low occupancy complexes at saturating LC8 concentrations with both human and Drosophila ASCIZ indicates that negative cooperativity is an important feature of ASCIZ-LC8 interactions. The prevalence of intrinsic disorder and multivalency among transcription factors suggests that formation of heterogeneous, dynamic complexes is a widespread mechanism for tuning transcriptional regulation.
Data availability
The chemical shifts for dLBD ASCIZ have been deposited in the Biological Magnetic Resonance Data Bank under accession code 27412 (http://www.bmrb.wisc.edu/data_library/summary/index.php?bmrbId=27412).
Article and author information
Author details
Funding
National Institute of General Medical Sciences (R01-084276)
- Elisar J Barbar
National Health and Medical Research Council (APP1026125)
- Jörg Heierhorst
National Institute of General Medical Sciences (R35GM124779)
- Steve L Reichow
National Institutes of Health (1S10OD018518)
- Elisar J Barbar
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Clark et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Multivalency regulates activity in an intrinsically disordered transcription factor
eLife 7:e36258.
https://doi.org/10.7554/eLife.36258
