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Jon Markert

@jonmarkert.bsky.social

Postdoc Harvard Medical School, cryo-EM, chromatin, transcription.

13 Posts165 Follower93 Folgt
Seychelle Vos@voslab.org · 3mo ago

⚡New preprint from the lab⚡: A key early checkpoint in gene expression is promoter proximal pausing of RNA polymerase II. For over 20 years, we as field have not been able to recreate pausing under realistic cellular conditions. @robertovn.bsky.social shows that ELOF1 is the missing piece.

Roberto Vázquez Núñez@robertovn.bsky.social · 3mo ago

🚨 New preprint: GATO-seq did it again! ELOF1 is the missing promoter-proximal factor that confers RNA Pol II resistance to TFIIF. Including ELOF1, DSIF, and NELF in GATO-seq reactions recapitulates promoter-proximal pausing in vitro at physiological conditions for the 1st time. tinyurl.com/ELOF1

Seychelle Vos@voslab.org · 7mo ago

🧪🧬New preprint We present cryo-EM structures of reconstituted CTCF–nucleosome complexes, showing CTCF dimerization drives nucleosome oligomerization into defined higher-order assemblies. Disrupting CTCF–CTCF interfaces in mESCs reduces looping and impairs differentiation. tinyurl.com/CTCF-nucleos...

Harvard Med Cell Biology@harvardcellbio.bsky.social · 11mo ago

New work from the Moazed lab reveals the requirements for establishment & epigenetic stability of mammalian heterochromatin! www.cell.com/molecular-ce...

Requirements for establishment and epigenetic stability of mammalian heterochromatin

Tatarakis et al. study how H3K9me3 heterochromatin is formed and inherited in mammalian cells. Using a synthetic heterochromatin assembly system and genetic screens, they uncover requirements for init...

cell.com

Felix Steinruecke@felixsteinruecke.bsky.social · last yr.

I’m excited to share my first paper in the Farnung lab, in which we report four cryo-EM structures of the human DNA replication machinery engaging with and progressing into a nucleosome.

Lucas Farnung@lucas.farnunglab.com · last yr.

🔬 New from the Farnung Lab: We established a fully in vitro reconstituted chromatin replication system and report the first cryo-EM snapshots of the human replisome engaging nucleosomes. Brilliant work by @felixsteinruecke.bsky.social with support from @jonmarkert.bsky.social! tinyurl.com/replisome

Jon Markert@jonmarkert.bsky.social · last yr.

Our work on DNA replication is out! Led by @felixsteinruecke.bsky.social, we monitor the replisome progressing into nucleosomes!

Lucas Farnung@lucas.farnunglab.com · last yr.

🔬 New from the Farnung Lab: We established a fully in vitro reconstituted chromatin replication system and report the first cryo-EM snapshots of the human replisome engaging nucleosomes. Brilliant work by @felixsteinruecke.bsky.social with support from @jonmarkert.bsky.social! tinyurl.com/replisome

Jon Markert@jonmarkert.bsky.social · last yr.

Take a look at our new collaboration project with the Phil Cole lab, we demonstrate how SIRT6 can recognize and remove a variety of different Histone acylations!

Lucas Farnung@lucas.farnunglab.com · last yr.

🚨New paper🚨Our new study with the lab of Phil Cole uncovers how SIRT6 dynamically adapts structurally and enzymatically to target diverse histone acylations (e.g., H3K27ac) within nucleosomes. @jonmarkert.bsky.social doi.org/10.1016/j.jb... #Chromatin #SIRT6 #CryoEM

Jon Markert@jonmarkert.bsky.social · last yr.

Are you interested in hearing this SETD2 story in more detail? I’ll be presenting it at @fnucleosome.bsky.social this week! Please see the poster for more details

Lucas Farnung@lucas.farnunglab.com · 2y ago

Ever wondered how transcription choreographs histone modifications? Our work reveals the basis of co-transcriptional H3K36me3 by SETD2. We visualize how a histone writer coordinates with the transcription machinery! This is the magnus opus of @jonmarkert.bsky.social! tinyurl.com/setd2

Basil Greber@bjgreber.bsky.social · last yr.

For our latest paper, we worked with SYROS Pharmaceuticals, the groups of Dylan Taatjes and Robin Dowell at CU Boulder, and @abhaykot.bsky.social. Junjie Feng in my lab determined the #cryoEM structure of the CDK7 inhibitor SY5609 bound to its target... www.science.org/doi/10.1126/...

TFIIH kinase CDK7 drives cell proliferation through a common core transcription factor network

CDK7 kinase activity is found to control RNAPII transcription through a cohort of TFs that drive cell cycle and proliferation.

science.org

Xiaoli Sky Wu@xiaoliwu.bsky.social · 2y ago

Very excited to bring GEARs back with @jonmarkert.bsky.social and @ara-latifkar.bsky.social. We look forward to seeing you in Goldenson 122, Harvard Medical School for our first seminar on 02/27, 6PM.

GEARs@gearseminar.bsky.social · 2y ago

After a long break, GEARs is back! We will feature three speakers on Feb 27th, 6PM in Goldenson 122. Please register via docs.google.com/forms/d/e/1F... so we can get enough food and drinks. You can nominate speaker sor volunteer for our future seminars through docs.google.com/forms/d/e/1F....

Seychelle Vos@voslab.org · 2y ago

Our collaborative AGO2 work with @bartellab.bsky.social is published! Abdallah and Peter used cryo-EM and biochemistry to determine the structure of AGO2 in a slicing competent conformation with a fully paired RNA. Read more about it here: tinyurl.com/AGO2-slicing

The structural basis for RNA slicing by human Argonaute2

Mohamed et al. report the cryoelectron microscopy structure of human AGO2 with fully paired guide RNA. Their analysis reveals the structural basis for the slicing activity that drives RNAi, showing that the slicing-competent conformation is achieved by domain movements and RNA-protein contacts distinct from those of conformational intermediates and prokaryotic homologs.

tinyurl.com

Lucas Farnung@lucas.farnunglab.com · 2y ago

Another highlight from our story: @jonmarkert.bsky.social uncovered how SPT6 binds the exposed H2A–H2B dimer during nucleosomal traversal by Pol II. AlphaFold helped tremendously in validating this interaction. tinyurl.com/setd2 Also check out our H2A–H2B screen: www.biorxiv.org/content/10.1...

SPT6 binds the H2A–H2B dimer.
Lucas Farnung@lucas.farnunglab.com · 2y ago

Ever wondered how transcription choreographs histone modifications? Our work reveals the basis of co-transcriptional H3K36me3 by SETD2. We visualize how a histone writer coordinates with the transcription machinery! This is the magnus opus of @jonmarkert.bsky.social! tinyurl.com/setd2

Jon Markert@jonmarkert.bsky.social · 2y ago

Pam taught me so much (how to make nucleosomes, how to use AKTAs…), I’m so incredibly grateful to have worked with her! The entire chromatin field is impacted by her, a very bittersweet day for the Luger lab! I wish her the best!!

Karolin Luger@nucleosomepolice.bsky.social · 2y ago

Saying goodbye to our lab manager of 25 years. we owe her EVERYTHING, she will be missed. To make sure she doesnt forget about #nucleosomes, we presented her with nucleosome art by the gifted Montana Fowler. also fun to hang out with current and many former lab members!

Di Jiang@dijiang319.bsky.social · 2y ago

Online today @science.org Structural basis of H3K36 trimethylation by SETD2 during chromatin transcription by @jonmarkert.bsky.social @lucas.farnunglab.com et al. at @harvardcellbio.bsky.social #cryoEM #chromatin #transcription #cryoEM #Pol_II🧪🧬❄️🔬 www.science.org/doi/10.1126/...

Structural basis of H3K36 trimethylation by SETD2 during chromatin transcription

During transcription, RNA polymerase II traverses through chromatin, and post-translational modifications including histone methylations mark regions of active transcription. Histone protein H3 lysine...

science.org

Lucas Farnung@lucas.farnunglab.com · 2y ago

Ever wondered how transcription choreographs histone modifications? Our work reveals the basis of co-transcriptional H3K36me3 by SETD2. We visualize how a histone writer coordinates with the transcription machinery! This is the magnus opus of @jonmarkert.bsky.social! tinyurl.com/setd2

Jon Markert@jonmarkert.bsky.social · 2y ago

With 8 composite cryo-EM maps (totaling 47 EMDB entries) and several biochemical assays, we demonstrate the mechanistic basis for the positioning of H3K36me3 within actively transcribed regions. Surprisingly, SETD2 must be relieved of auto inhibition by the transcription machinery!

Lucas Farnung@lucas.farnunglab.com · 2y ago

Ever wondered how transcription choreographs histone modifications? Our work reveals the basis of co-transcriptional H3K36me3 by SETD2. We visualize how a histone writer coordinates with the transcription machinery! This is the magnus opus of @jonmarkert.bsky.social! tinyurl.com/setd2

Ben Garcia@garcialabms.bsky.social · 2y ago

A great collaboration with Phil Cole (Harvard) engineering Sortase to facilitate its transpeptidase activity on histone H3 has been published in JACS. This work developed multiplexed "cut-and-paste" middle-down proteomics with tandem mass tags for quantification. pubs.acs.org/doi/full/10....

Circular Engineered Sortase for Interrogating Histone H3 in Chromatin

Reversible modification of the histone H3 N-terminal tail is critical in regulating the chromatin structure, gene expression, and cell states, while its dysregulation contributes to disease pathogenesis. Understanding the crosstalk between H3 tail modifications in nucleosomes constitutes a central challenge in epigenetics. Here, we describe an engineered sortase transpeptidase, cW11, that displays highly favorable properties for introducing scarless H3 tails onto nucleosomes. This approach significantly accelerates the production of both symmetrically and asymmetrically modified nucleosomes. We demonstrate the utility of asymmetrically modified nucleosomes produced in this way in dissecting the impact of multiple modifications on eraser enzyme processing and molecular recognition by a reader protein. Moreover, we show that cW11 sortase is very effective at cutting and tagging histone H3 tails from endogenous histones, facilitating multiplex “cut-and-paste” middle-down proteomics with tandem mass tags. This cut-and-paste proteomics approach permits the quantitative analysis of histone H3 modification crosstalk after treatment with different histone deacetylase inhibitors. We propose that these chemoenzymatic tail isolation and modification strategies made possible with cW11 sortase will broadly power epigenetic discovery and therapeutic development.

pubs.acs.org