New #preprint from the Basu & Stewart labs! We discover a non-catalytic role for H3K4me3 methyltransferase MLL2 in modulating 3D chromatin organisation and mobility as pluripotent cells are primed for differentiation.

Location: Flowers building G47A. 15:30: Annabelle Wurmser: “Capturing chromatin dynamics during neuromesodermal progenitor specification” . 16:00: Daniela Dietrich (University of Bristol) – “Hydrotrotropism – how roots search for water". 17:00 Social Happy Hour (SEC, 7th floor).

This Friday 27th June, we have another exciting set of talks at our monthly Cell and Developmental Biology Networking Event @ImperialLifeSci with Daniela Dietrich @dnl_dietrich joining us from Bristol and our very own Annabelle Wurmser from my lab. Please do join us!.

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Look forward to hearing feedback from the field!.

Thanks also to our collaborator labs for all their help on this: Samarajiwa, Huntly, @KlenermanLab @David_Holcman @BertieGottgens @PradeepMadapura @imohorianu.

Huge congrats to first authors @MaikeSteindel & Oliver Davis! This has also been quite the team effort from the whole lab: Liviu, Shuyue, @gokceagsu @DeepAdhyaPhD @jorgmorf @AnnabelWurmser @StanStrawbridge @SCICambridge @ImperialLifeSci.

Using single-molecule imaging, we find that MLL2 acts like a tether, restricting chromatin mobility genome-wide and at the Mll2-dependent gene Sox2. This suggests a model where MLL2 tethering increases enhancer-promoter mixing at key neuroectoderm genes to drive differentiation.

Micro-C reveals that MLL2’s effect on chromatin architecture is more substantial, stabilising enhancer-promoter loops associated with bivalent genes in primed pluripotent cells. Interestingly, MLL2’s catalytic activity is not required for loop formation or differentiation.

However, single-cell transcriptomics and quantitative immunofluorescence of the priming transition reveal that MLL2 has only a subtle change on transcription, increasing the expression of a few important neuroectodermal transcription factors such as SOX2.