Thread by @Feli_Bas

A new job, a #pig, a pregnancy, a move, a pandemic, 5(6) rev and many #pampers later, I’m delighted to share my co-first authorship with @KellerValsecchi in the @AsifaAkhtar1 lab today in @nature. Thread below for summary nature.com/articles/s4158…

In this crazy journey we reconstituted the minimal #Drosophila requirements to achieve #Xchromosome targeting

We systematically asked the hierarchical interdependencies of the known MSL complex members to understand the contribution of #DNAmotif, #interaction_partners and #evolutionary determinants in the process of targeting the single male #Xchromosome for transcriptional upregulation

The complex genetic analysis performed didn’t make much sense in the beginning. But all got in a new light when doing evolutionary protein domain scanning we could figure out a peculiar genetic interaction within the c-term of MSL2 and the ncRNA roX2

Indeed such Drosophila protein-specific intrinsically disordered region was able to induce aggregation of the ncRNA roX (yes I’m refusing to say #Phase S.. word). This is an atypical extremely stable interaction shared with few other proteins in the cellular proteome

As studying dying larvae (any alteration of such interaction was lethal) is a “dead end” and in vitro analysis are too biased (pre-existing knowledge) we decided to use a completely heterologous system and reconstitute piece by piece the components necessary to find the targets

Yes instead of looking for what was missing in mutants dm, we started to add pieces to puzzle in mESCs to see when finally we see transcriptional activation.After more than 50 endo-tagged cell lines (without counting all the other variables tested negative and not publishable :()

we could show that local cis condensation of this two components MSL2-CTD and roX2 RNA creates a glue which stabilizes the complex at the region of ncRNA syntesis and allows chromatin to be acetylated and neighboring active genes to be fine-tuned within a range of ~30Kb.

Finally we wanna thank the @mpi_ie and #akhtarlab for the great work atmosphere over the years. Send a virtual hug to @AsifaAkhtar1 for believing in it and fighting like tiger against #reviewer2 until the end, when we couldn't anymore

A big thank to our husbands which never stopped hating but supporting this “pamper” journey
Thanks to best collaborator ever @KellerValsecchi who took my “we willl never gonna go through in Nature” as a bet and this time she won.

The cute original draft for a "model" for the initial manuscript :) done by awesome @JanineSeyffert