…is the title of our new review that is going to appear in Trends in Biochem Sci very soon. A sneak preview is here. In the paper – shaped by Xavier and Jason – we ponder on the observation that multiple paralogues are observed for all members of our favourite chromatin remodelling complex – the Nucleosome Remodelling and Deacetylase (NuRD) complex. This phenomenon has been observed for other remodelling complexes too (and likely many other types of protein complex).
A couple of recent papers provide data that point to NuRD assemblies that are composed of a specific paralogue combination. This paper by Dan Bauer’s group is the best example – they observe that repression of the fetal gamma globin gene depends strongly on the NuRD complex – but on a specific variant containing CHD4, GATAD2A, HDAC2, MBD2 nd MTA2 – and not their paralogues… They have multiple lines of evidence to support this idea.
We sift through several large-scale studies (quantitative proteomics and genome-wide CRISPR knockouts in >1000 cancer cell lines) to hint that there are trends in which paralogues are more or less important in different tissues and in which subunits are more or less likely to be found with others. From this meta-analysis, we propose that different NuRDs might do different jobs in different places at different times… Super job by Xavier in particular in crunching a lot of big datasets to distill them down to tantalizing observations….
