Anders Sejr Hansen

On the left - western blot of B16F10 cells wt and KO for CDK8. Our in house produced antibodies give a lot of unspecific bands. On the right same probes with antibodies preincubated with fixed CDK8 KO cells - there is a specific band and faint unspecific bands, which can be probably eliminated with increase of amount of KO cells.

Neat trick if you polycolonal ab's suck. Incubate them with fixed cells with a KO of your protein of interest, then spin. Protocol here: www.med.upenn.edu/markslab/ass...
I was amazed how well it worked on first try (I'm sure that I can completely eliminate unspecific bands)
#WesternBlot #cellsky

Happy #FluorescenceFriday! Our #CellLineOfTheWeek is SMC (structural maintenance of chromosomes) protein 1A! 🧬🛠️

Our cell lines & plasmids are available for just the cost of shipping to reduce the barriers to scientific discovery.

📦 Dist. by @coriellinstitute.bsky.social & @addgene.bsky.social

A human-specific regulatory mechanism revealed in a pre-implantation model Nature - Genetic manipulation of blastoids reveals the role of recently emerged transposable elements and genes in human development.

Today in @nature.com, we present our work leveraging functional genomics and human blastoids to uncover a human-specific mechanism in preimplantation development driven by the endogenous retrovirus HERVK.
Special thanks to the reviewers whose comments improved our manuscript a lot! rdcu.be/eI3tD

Some proteins are primarily regulated by one mechanism: RNA abundance, translation, or clearance.

The regulation of most proteins is dominated by different regulatory mechanisms across cell types.

Gratifyingly, this complex regulation defines simple rules ⬇️

www.biorxiv.org/content/10.1...

Huntington's disease successfully treated for first time One of the most devastating diseases finally has a treatment that can slow its progression and transform lives, tearful doctors tell BBC.

New cures feel sudden, but the seeds were planted decades ago by basic scientists.

Which seeds will turn into cures? Unpredictable looking forward, a straight line looking back. 🧪🧬 🧵

It's also nice to see a very rigorous and careful approach to analyzing interactions in live-cell imaging data subject to noise. Direct simple thresholding of such data will inevitably give artefactual numbers.

Really enjoyed reading the new @lucagiorgetti.bsky.social lab preprint that makes the case that not all E-P interactions are created equal - it is the subset of long-lived extrusion-mediated E-P interactions that are most transcriptionally important:
www.biorxiv.org/content/10.1...

That was >40 years ago!

So many of John's papers still read incredibly prescient to this day.

Fun fact, John is still around and scheduled to give his faculty talk to my department this Wednesday.

Amazing. Thanks for sharing.

Asking BlueSky for help: For a review, I am trying to accurately credit the first paper that measured pairwise 3D distances between 2 pieces of DNA on the same chromosome (or cosmid). Is Trask 1989 the first?
I know of earlier single-locus papers (1982).
www.sciencedirect.com/science/arti...

Jamie Drayton and I were fortunate to contribute some RCMC analyses to this beautiful paper from Eder, Moene...van Steensel that systematically maps the relationship between enhancer location and gene expression (and nice to see RCMC predict expression in Fig 2H-I):
www.science.org/doi/10.1126/...

Excited to share another new preprint from our lab in which we developed a cluster-based phasing strategy using long read nano-NOMe-seq data to link distinct CTCF binding states—captured at the single molecule level—to the transcriptional status of genes: biorxiv.org/content/10.1...

Speaker Spotlight: Don’t miss @Anders_S_Hansen from MIT as he unpacks the secrets of distal gene regulation in space and time! Learn how enhancers find and activate their target genes—revealing new insights into the selectivity and dynamics of gene control. Reserve your seat:

Is enhancer-driven gene regulation all wrapped up? - Nature Reviews Genetics In this Comment, Wendy Bickmore discusses mechanistic models of how 3D genome organization facilitates communication between distant enhancers and their target promoters to regulate gene expression.

Very interesting new @wbickmor.bsky.social commentary on the mechanistic mystery that is very distal enhancer-promoter interactions www.nature.com/articles/s41...

The dynamics of centromere assembly and disassembly during quiescence Quiescence is a state in which cells undergo a prolonged proliferative arrest while maintaining their capacity to reenter the cell cycle. Here, we analyze entry and exit from quiescence, focusing on h...

New preprint! Graduate student Océane Marescal leverages quiescence - proliferative hibernation - to reveal unexpected dynamics for “constitutively”-localized centromere proteins. To understand the logic of cell division, you need to consider non-dividing cells.

www.biorxiv.org/content/10.1...

This is a fantastic review

PDS5 proteins control genome architecture by limiting the lifetime of cohesin-NIPBL complexes Cohesin-NIPBL complexes extrude genomic DNA into loops that are constrained by CTCF boundaries. This process has important regulatory functions and weakens the separation between euchromatic and heter...

Excited to share our preprint w/Gordana Wutz, Iain Davidson, Leonid Mirny, Jan-Michael Peters
www.biorxiv.org/content/10.1...
Evidence that PDS5A/B limits NIPBL-cohesin life w/effects on CTCF boundaries & chrm compartments, +mechanisms of compartment-extrusion interplay & cohesin regulation by PDS5

Widespread epistasis shapes RNA polymerase II active site function and evolution - Nature Communications The active site of RNA Polymerase II is highly conserved. Here the authors show that mutations can propagate effects across the enzyme and alter genetic behavior of distal residues, demonstrating plas...

Final version of Bingbing Duan’s main thesis work is out now now in Nature Communications @natureportfolio.nature.com www.nature.com/articles/s41... I’m so pleased with this study that we’ve been working on for so long #epistasis #transcription #geneexpression 1/

Fine structural organization of the interphase nucleus in some mammalian cells, Monneron & Bernard, 1969

Gotta love these classic papers about nuclear architecture. In hindsight, all that we understand and discover today was already contained in their images.

www.sciencedirect.com/science/arti...

(1/n) DNA-PAINT imaging inside the nucleus at single antibody resolution using TIRF? Ultrathin sectioning makes it happen!

Grateful to share my postdoctoral work introducing “tomographic & kinetically-enhanced DNA-PAINT” or in brief: tkPAINT. Out in @pnas.org!
doi.org/10.1073/pnas...
👇🧵

Congratulations to Masahiro Nagano on his new paper on STAG3-cohesin.

STAG3-cohesin has a much shorter residence time which leads to altered 3D genome organization and STAG3-cohesin is important for male germ cell differentiation.
www.nature.com/articles/s41...

Today, I would like to honor the memory of Roger Y. Tsien, who died on August 24, 2016. His legacy lives with all who use his technologies, including calcium sensors, fluorescent proteins, the acetoxymethyl (AM) ester, & many more! #FluorescenceFriday
www.nature.com/articles/nme...

Normatively, I also think it makes sense to spread funds so labs can keep running. I am fortunate to have not lost existing grants and have enough to support my current group. The situation at e.g. Harvard, Northwestern with grants getting pulled is infinitely worse and breaks my heart.

This ended up getting way more attention than I intended.
@drugmonkey.bsky.social ’s post was about how it FEELS. My reply was intended to be descriptive, not normative. As in, it subjectively “feels” bad to have these grants go unfunded. E.g. R21 was 3rd attempt: ND -->50%-->4%-->unfunded-->sad

Out today in @nature.com: Together with the Honigmann, Shevchenko, Drobot and Hof labs, we present a general workflow for imaging the localization and transport of individual lipids in cells and mapping their metabolism.
www.nature.com/articles/s41...

The NHGRI PO kindly indicated that there might be a chance of FY26, but of course very difficult to predict how things will go in the future. The PO has been very kind and is clearly working under difficult circumstances. Situation at other institutes could be very different as well.

I have
NIGMS R35, impact score 12
NIHGRI R21, 4th percentile
NHGRI R01, 7th percentile (co-I)
and it seems like none will be funded. 0/3.

PO (who has been very helpful) said "Unfortunately, I do not expect this application will be selected for funding in FY25."

😭

NIPBL dosage shapes genome folding by tuning the rate of cohesin loop extrusion Cohesin loop extrusion is a major driver of chromosome folding, but how its dynamics are controlled to shape the genome remains elusive. Here we disentangle the contributions of the cohesin cofactors ...

New preprint with @gfudenberg.bsky.social

We find the rate of cohesin loop extrusion in cells is set by NIPBL dosage and tunes many aspects of chromosome folding.

This provides a molecular basis for NIPBL haploinsufficiency in humans. 🧵👇

www.biorxiv.org/content/10.1...

Extra kudos and thanks to all the staff at NIH and NSF and other federal funding agencies for working extra hard in very small windows of opportunity to get grants reviewed and funds released before the attention-addled federal policies change again (on an hourly basis).

Contrasting photographs of the night-time skylines of Manhattan (left) and Nijmegen (right), with matching genome-wide association plots underneath each.

Not sure who came up with "Manhattan Plot", but in 2014 I coined the alternative term "Nijmegen Plot" (inspired by the Dutch town where I live) to describe underwhelming results from our earliest genome-wide association scans of language/reading traits.