Pradeepa Madapura
@pradeepmadapura.bsky.social
Scientist/Professor of Chromatin & Genome Regulation, Blizard Institute, @QMULepigenetics; views are my own. https://www.madapuralab.net/home
Check this out: Cell-type-specific changes in chromatin mobility, accompanied by 3D genome reorganisation, loss of PcG-associated interactions and emergence of CDX2-associated interactions. Study by @srinjan.bsky.social team. Happy to contribute. www.biorxiv.org/content/10.6...
What’s next in transcription and chromatin biology? Find out in York, 18–20 November, as researchers come together to share the latest breakthroughs in epigenetics, genome organisation and transcriptional regulation. Book your place. https://www.eventsforce.net/biochemsoc/286/register
Very happy to see this story finally out in @natbiotech.nature.com: www.nature.com/articles/s41... Fantastic collaboration with @lancasterlab.bsky.social on how to identify and ‘fix’ differentiation-compromised human pluripotent stem cells. @babrahaminst.bsky.social @mrclmb.ac.uk 🧵 below
Reversible epiblast regionalization determines differentiation potential of human pluripotent stem cells - Nature Biotechnology
The differentiation variability of human pluripotent stem cell lines is diagnosed and corrected.
nature.com
I am on paternity leave but I need to talk about this work by the @andersshansen.bsky.social lab that was published @natsmb.nature.com. The authors provide absolute quantification of chromatin loops across the genome. www.nature.com/articles/s41... Putting actual numbers in E-P, P-P and all loops!
Genome-wide absolute quantification of chromatin looping - Nature Structural & Molecular Biology
By calibrating Micro-C against live-imaging data in mouse embryonic stem cells, Jusuf et al. quantified 65,929 chromatin loops genome-wide, finding that most loops form pairwise interactions with an a...
nature.com
🆕 review with @jpunfried.bsky.social out in Nature SMB. Direct roles of lncRNAs in transcriptional activation. What do we understand about how lncRNAs lure Pol2 and set the stage for RNA production, and what do we still miss? www.nature.com/articles/s41...
Direct roles of long non-coding RNAs in transcription activation - Nature Structural & Molecular Biology
This Review discusses how long noncoding RNAs (lncRNAs) control transcription activation by RNA polymerase II, including how they are produced at active enhancers or chromatin-domain boundaries and ac...
nature.com
Join us this Wednesday to hear about fascinating research from @kashyapchhatbar.bsky.social and @a-radzisheuskaya.bsky.social! If you're not already registered, click here to sign up: us06web.zoom.us/webinar/regi... you can also join the conversation at our discord: discord.com/invite/dXqT89r
🧵 CTCF is essential for embryonic development, but why has remained unclear. By combining gastruloids with a temporal degron system, we uncovered a surprising dual function — and it changes how we think about CTCF's role in development. 1/8 www.biorxiv.org/content/10.6...
A dual role for CTCF in development
CTCF is an essential DNA binding protein whose absence leads to embryonic lethality. CTCF is primarily known for its role in 3D genome organization where its N-terminal domain interacts with cohesin to anchor chromatin loops. How CTCF facilitates proper embryonic development remains unclear, necessitating temporal control to resolve its stage-specific functions. By combining gastruloids, an in vitro model of embryonic development, with a degron system to rapidly deplete CTCF at defined timepoints, we show that early CTCF depletion impairs early gastruloid morphogenesis. Surprisingly, ATAC-seq and time-resolved RNA-seq revealed that differentiation was unaffected. CTCF binding is strongly enriched at promoters of downregulated genes. Re-expression of a CTCF variant with an N-terminal truncation, incapable of looping, was sufficient to rescue the expression of CTCF-promoter bound genes and the defects in morphogenesis. However, extended culture (up to 168 hours) of gastruloids reconstituted with N-terminal truncated CTCF led to their collapse. Our work shows that CTCF has a dual function in early mammalian development: at early stages CTCF regulates developmentally important genes through promoter binding, while at later stages its looping function is required for correct development. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, https://ror.org/0472cxd90, 637587, 865459 Dutch Research Council, https://ror.org/04jsz6e67, 016.161.316, VI.C.222.049 Dutch Cancer Society, https://ror.org/0368jnd28, N/A
biorxiv.org
Delighted to share our latest work in @narjournal.bsky.social on the importance of (lnc)RNA–protein interactions in cell division, and how we identified RSRC2 as a new RBP involved in splicing and centrosome-associated RNA localisation academic.oup.com/nar/article/...
RSRC2 is a novel RNA-binding protein that safeguards mitotic fidelity by interacting with the lncRNA C1QTNF1-AS1
Abstract. Mitotic fidelity requires proper chromosome alignment at the spindle equator, a process known as chromosome congression, mediated by well-establi
academic.oup.com
We are excited to be recruiting into 3 Associate Professorship's in @oxfordbiochemistry.bsky.social. Come join us as a colleague and benefit from our vibrant and multidisciplinary environment. Reach out to me if you have any questions. Please repost! (tinyurl.com/48deybuu) (tinyurl.com/4pdvjaft).
That's quite the bucket (vat?) Just when I thought I couldn't despair of UKRI any more. This is no way to run a call, let alone one with funding of this magnitude.
Kirsty Grainger @kirstygrainger.bsky.social · 8mo agoCan anyone think of an example of government spend of this magnitude and speed (excluding covid)?? 4 weeks from call announcement to submission (no advance warning) and within that only 2 weeks to flag your intention to submit. £40M total - individual awards £9.4M www.ukri.org/opportunity/...
Exited to share Current Opinion review on how chromatin hubs involving multiple enhancers and promoters are formed, and their potential roles in gene regulation: www.sciencedirect.com/science/arti...
It super exciting how quickly tools to unlock #IDR function are developing- can't wait to give this a try!! Congrats again!
Alex Holehouse@alexholehouse.bsky.social · 8mo agoPapers are like buses... You wait for ages, then two come along at once. Huge congrats to @bornanovak.bsky.social and @jefflotthammer.bsky.social for pushing and driving every aspect of this work, preprinted ~1 year ago to the day (Friday before BPS), now published! www.nature.com/articles/s41...
We missed scoring 96 this round! Scoring 17000 applications and making decision is not a easy task. Better go with lottery model after prescreening.
Duncan Sproul@sproullab.bsky.social · 8mo agoVery interesting plot for those interested in the #MSCA postdoc fellowships.
Check out our new findings showing BRD4's role in preventing the premature activation of developmental transcription factors via #Polycomb, providing new mechanistic insights into the pathogenesis of neurodevelopmental disorder #CdLS #NDDs, #chromatinopathies www.biorxiv.org/content/10.6...
Spend months during last summer writing a MRC grant, hoping that we will have finding to continue employing postdocs in the lab. This week l am already expecting to receive a disheartening message from UKRI.
Mark A. Hanson@hansonmark.bsky.social · 9mo agoBoth MRC and BBSRC responsive modes now withdrawn until further notice. Existing applications unlikely to succeed (late 2025 round expecting 1-5% success rate). Listen, I get that UKRI wants to pivot. But killing both at once is devastating. Let's hope at least one opens by summer... #AcademicSky
At a time when the UK should be capitalising on its global reputation as a great place to do science, this is an enormous own goal. I am so sorry for all those who jobs are going to be impacted.
Mark A. Hanson@hansonmark.bsky.social · 9mo agoBoth MRC and BBSRC responsive modes now withdrawn until further notice. Existing applications unlikely to succeed (late 2025 round expecting 1-5% success rate). Listen, I get that UKRI wants to pivot. But killing both at once is devastating. Let's hope at least one opens by summer... #AcademicSky
We need to be shouting about the effects of this on junior researchers from the roofs, writing to our MPs. We are risking a "missing generation" of researchers.
Mark A. Hanson@hansonmark.bsky.social · 9mo agoBoth MRC and BBSRC responsive modes now withdrawn until further notice. Existing applications unlikely to succeed (late 2025 round expecting 1-5% success rate). Listen, I get that UKRI wants to pivot. But killing both at once is devastating. Let's hope at least one opens by summer... #AcademicSky
I have grant under consideration and I have already given up on this round :(
Ian Sudbery@iansudbery.bsky.social · 9mo agoI'm seeing relatively little chatter or outcry about what is happening at the MRC, the UK's biomedical research funder. Before Christmas MRC paused the acceptance of many of its grants, including the standard applicant-led research grant. There has been no public information on what is happening 🧵
How could you reveal this on social media? Did you not sign a naan-disclosure agreement?
Michael Hoffman@michaelhoffman.bsky.social · 9mo agoWhat genetic change to Indian wheat led to superior baking in a tandoor? A naan sense mutation
Happy to share with you our work on how the interferon response impacts embryonic development 🦠Mammalian embryos contain endogenous dsRNAs that resemble viruses and can be misrecognised by the dsRNA sensor MDA5. Thanks to all collaborators, we could not have done it without you 🤩 rdcu.be/eWMfA
Double stranded RNA sensing is silenced during early embryonic development
Nature Communications - The type I interferon response is suppressed during early development, making embryos susceptible to pathogens. Here, the authors show that this suppression contributes to...
rdcu.be
A human embryo implantation model from the @Rugg-Gunn Lab *key for understanding the early extraembryonic-maternal interactions Congrats to everyone involved! It’s been great to see this project develop. Huge credit to the @babrahaminst.bsky.social authors 🥂🍾 www.cell.com/cell/fulltex...
Modeling human embryo implantation in vitro
Building an in vitro model of receptive endometrium allows investigation of human embryo implantation and early post-implantation development and recapitulates the earliest stages in establishing the ...
cell.com
Babraham Institute@babrahaminst.bsky.social · 10mo agoLearn more about this research in our interview with Peter Rugg-Gunn 🧪 youtu.be/2NYsWPp1UYk?...
The TArgeted Cohesin Loader (TACL) paper was just published. Happy that we were able to contribute to this really exciting project! If you want to learn how targeting cohesin to defined loci in the genome affects the local chromatin environment and transcription, look no further! rdcu.be/eLiT5
Characterization of induced cohesin loop extrusion trajectories in living cells
Nature Genetics - This study introduces a system called TArgeted Cohesin Loader (TACL) that recruits cohesin complexes at defined genomic regions and induces loop extrusion events in living cells,...
rdcu.be
We have added additional functionalities including a collapsible protein pane and zoom scrolling. domaindesigner.farnunglab.com
Lucas Farnung@lucas.farnunglab.com · last yr.New week, new tool: Find our Protein Domain Designer tool to generate publication-ready protein domain diagrams here: domaindesigner.farnunglab.com
Many enhancers that drive tissue-specific gene expression are already connected to gene promoters in human pluripotent cells. In a new preprint, we share some clues about when, how, and why this happens! www.biorxiv.org/content/10.1...
Poising and connectivity of emergent human developmental enhancers in the transition from naive to primed pluripotency
In primed human pluripotent stem cells (hPSCs) resembling post-implantation epiblast, numerous lineage-specific enhancers assume the poised chromatin state, co-marked by H3K4me1 and Polycomb-associate...
biorxiv.org
Histone acetylation - not always about transcriptional activation: H4K16ac safeguards the genome replication program by repressing premature replication of heterochromatin. Well done Marta Milan! tinyurl.com/yuy9m8t3
