DNA-binding, multivalent interactions and phase separation in transcriptional activation
Ngaio C. Smith
A and Jacqueline M. Matthews A *
+ Author Affiliations
- Author Affiliations
A School of Life and Environmental Sciences, Building G08, The University of Sydney, Darlington, NSW 2006, Australia.
Ngaio Smith obtained her BSc (Hons) and PhD from the University of Sydney under the supervision of Professor Jacqui Matthews. Her work focusses on the interactions of transcription factors and DNA, particularly in the LIM-HD family of proteins. A key area of interest of her work has been how protein–protein interactions affect DNA-binding specificity and gene regulation. |
Jacqui Matthews is a graduate of UNSW and was awarded her PhD from the University of Cambridge, working with Sir Alan Fersht to define the principles underlying protein folding. She undertook postdoctoral work with Professor Richard Simpson at the Ludwig Institute for Cancer Research in Melbourne, where she first met and worked with Ed Nice. She developed an independent research program at The University of Sydney centered on biomolecular interactions, particularly the assembly of multiprotein transcriptional complexes involved in cell-specific transcriptional regulation. |
Australian Journal of Chemistry 76(8) 351-360 https://doi.org/10.1071/CH22269
Submitted: 21 December 2022 Accepted: 6 April 2023 Published: 5 July 2023
© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND)
Abstract
Transcription is an essential process in biology whereby gene-specific transcription factors target sites on DNA to recruit the basal transcription machinery that will produce messenger RNA (mRNA). It is a highly regulated multi-step process that involves many proteins and protein complexes. Transcription factors, the proteins that mark genes for activation, and other transcriptional regulators are highly enriched in low-complexity disordered regions, which are strongly linked to multivalent binding and phase separation. These disordered regions can form multivalent dynamic complexes that are essential for many aspects of transcription. Many of these proteins can phase separate in vitro and show evidence of phase separation in vivo. Whether these interactions represent biologically relevant phase separation in vivo is controversial. However, what these events do demonstrate is that many transcriptional proteins co-cluster with other factors in vivo, forming multivalent dynamic clusters that contribute to transcriptional events. We review some of these recently investigated events and consider how they contribute to our understanding of transcription.
Keywords: DNA binding, dynamic hubs, intrinsic disorder, liquid–liquid phase separation, multivalent interactions, protein–protein interactions, transcription factors, transcriptional activation.
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