The Lewis Lab

Chromatin biochemistry and genomics in development and cancer.
@UWMadison @UWSMPH @BMC_UW

[The Lewis Lab @PeterLewisLab]

New preprint from our lab! An H3.3 knockout does two things at once: it removes H3.3 from chromatin and destabilizes DAXX. We disentangle those functions and find that DAXX-mediated H3.3 deposition can be uncoupled from ERV silencing.
https://t.co/VvCD7CWmja

[The Lewis Lab @PeterLewisLab]

In a genome not so far away, the most elegant design in the galaxy was already wrapped into ~147 base pairs. #HappyNucleosomeDay, May-The-Fourth Be With You.

[The Roberts Lab @TheRobertsLab1]

Excited to share our latest study in @NatureComms where we uncover a new mechanism of chromatin regulation that is essential in certain SWI/SNF-mutant cancers. Congrats to @HaydenMalone3 and coauthors! #SWISNF #cancer (1/8)
@stjuderesearch @stjudegraduate
https://t.co/fQ96s3iXjS

[Hironori Funabiki @HironoriFunabi1]

Excited to share our structural insights into how microtubules differentially guide phosphorylation of kinetochore-microtubule regulators, Ndc80 and MCAK, for chromosome segregation. Heroic efforts by Yiming Niu with a fun collaboration with DeLuca lab!
https://t.co/bdQftOqQ1B

[Marta Markiewicz-Potoczny @PotocznyMarta]

Our latest research is now out in @NatureCellBio https://t.co/I3qN9dMG7o
We show that nonsense-mediated mRNA decay (NMD) pathway safeguards #telomere integrity in pluripotent #stemcells

[Keiichi Ito @itok10918]

A single-nucleotide enhancer mutation overrides chromosomal sex to drive XX male development | Nature Communications https://t.co/IaEP8zCiLJ

[Waggoner Lab @LabWaggoner]

Preprint: The tumour suppressor RBM5 activates the helicase DHX15 to regulate splicing
https://t.co/sKyserFIif @UCLA

[Kazuhiro Maeshima @kazu_maeshima]

Our linker histone H1 paper is out @ScienceAdvances: https://t.co/fGZsmvRPWK
@MasaAShimazoe et al. reveal that H1 acts as a liquid-like "glue" to organize chromatin in living cells. 🎉 Fantastic collab with @rcollepardo, @janhuemar, Charlie Phillips and others—huge thanks! 🙌 ½

[Timothy En Haw Chan @timothykoala]

How to make a heterochromatin by major satellite repeats transcripts?
Congrat @AleciaYHLO and Thomas Jenuwein lab for the work.

https://t.co/VQQzPSKUPZ

[Epigenome Technologies Inc. @EpigenomeTech]

Epigenetics Update - Accessory subunits of PRC2 mimic H3K27me3 to restrict the spread of Polycomb domains https://t.co/doyD9dy7Vt

Edwina McGlinn & Chen Davidovich in Mol Cell

#Epigenetics #PRC2 #H3K27me3
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Perfect for cancer, immunology, and aging; https://t.co/WmSYDGWPJD

[The Lewis Lab @PeterLewisLab]

These separation-of-function mutants show that H3.3 deposition can be uncoupled from ERV silencing. This supports our finding that H3.3 deposition at ERVs is dispensable for repression. Instead, repression depends on the C-terminal SIM and interaction with SUMOylated effectors.

[The Lewis Lab @PeterLewisLab]

New preprint from our lab! An H3.3 knockout does two things at once: it removes H3.3 from chromatin and destabilizes DAXX. We disentangle those functions and find that DAXX-mediated H3.3 deposition can be uncoupled from ERV silencing.
https://t.co/VvCD7CWmja

[The Lewis Lab @PeterLewisLab]

Which DAXX functions are required for ERV silencing? Mutants defective in ATRX binding or H3.3 deposition restore ERV repression. By contrast, deletion of the SIM abolishes silencing. Thus, ERV repression requires the C-terminal SIM, but not ATRX binding or H3.3 deposition.

[The Lewis Lab @PeterLewisLab]

Model: Gcn5-containing HAT complexes are targeted to active genes by the transcription machinery, providing a direct link between histone acetylation and gene activation. A fitting paper to revisit 30 years later, on what would have been Dave Allis's 75th birthday, March 22.

[The Lewis Lab @PeterLewisLab]

Happy 30th birthday to this paper published March 22, 1996, one of the foundational studies in chromatin biology. Brownell et al. linked a transcription-associated Tetrahymena HAT to yeast Gcn5p, providing a biochemical link for chromatin modification to gene activation.

[The Lewis Lab @PeterLewisLab]

And then decisive experiment. Recombinant Gcn5p expressed in E. coli had HAT activity in the in-gel assay, whereas controls lacked activity. With that, Gcn5p was assigned a direct biochemical activity, linking histone acetylation more directly to transcriptional activation.