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The first paper from my lab was published last week in Nature Genetics @NatureGenet. The main finding is that phosphorylation on a serine that is unique to H3.3 promotes p300 activity and enhancer acetylation. nature.com/articles/s4158…
This work started from an observation that H3.3 KO ESCs generally have less H3K27ac than wild-type ESCs, both globally and at enhancers. 
The first surprise - this happens without changing the "open" state of these regions or the level of p300 recruitment. So, something about H3.3 stimulates p300 activity.
We looked at differences in the H3.3 sequence compared to canonical H3. The only difference in the tails is at position 31 - H3.3S31 (a phosphorylation site!) vs H3A31. Addback experiments show that H3.3S31 is needed to restore H3K27ac in the H3.3 KO cells.
Inhibiting the reported kinase for H3.3S31 also reduced H3K27ac levels at enhancers.
We expected that this would be a phos/ac cis crosstalk. The second surprise - H3.3S31ph stimulates p300 activity on *other* nucleosomes in a trans mechanism.
Since the H3.3 KO ESCs lose ~50% of H3K27ac, we thought we might observe global effects on transcription. The third surprise - H3.3 KO ESCs can tolerate reduced H3K27ac and do not experience global reductions in transcription.
The problem comes when we ask cells to change their transcription program. In this case, we find that the H3.3 KO cells can't effectively activate enhancers during differentiation.
We think this study is important because (1) it suggests that H3.3 acts to integrate signaling information through a highly conserved residue (present on two independent genes and throughout evolution) to promote changes in transcription;
and (2) it raises fundamental questions about roles of chromatin states found at enhancers in gene activation versus the maintenance of transcription.
I am incredibly proud of and grateful to Sara Martire @SaraMartire for leading this project. She's a great catch for anyone looking for an amazing new faculty member and colleague this fall.
We couldn't have done this work without Aishwarya Gogate @aishwaryagogate. She's an exceptionally talented computational biologist now at Seattle Children's and we miss her dearly.
Amanuel Tafessu @amanuel_MT was also instrumental to this study - look forward to his insightful work explaining these observations in more detail.
And a big congratulations and thank you to the other co-authors, Amanda Whitmill, Jennifer Nguyen, Yu-Ching Teng @chingchingteng, and Melodi Tastemel @melodi_tastemel.
I can't say how great it was to work with Tiago Faial at Nature Genetics (I hear the music starting telling me to exit stage right...).
Finally, thank you to DISD for ending the school year just in time for me to be here when the paper came out last Friday.
