Krzysztof Herka

Beyond carrying out vital research, our staff are involved in lots of science outreach activities every year.

Recently, we hosted pupils for our annual Careers Lab. This programme is designed to inspire the next generation of STEM scientists & supporters.

More: www.cruk.cam.ac.uk/students/car...

Thank you @stefanschoenfelder.bsky.social - far too modest!

Flynn Lab FLYNNLAB Chromatin biology

Many thanks especially to Colm Doyle (now at @embl.org), who began this work with his beta globin locus study and @seanflynn.bsky.social (now of sites.google.com/view/flynnlab/ at @exeter.ac.uk - great things to come) for an incredible journey, as well as all authors at @cruk-ci.bsky.social! 9/9

....then edited them out to show how the regulation of genes in 3D contact was affected. 8/9

Improved simultaneous mapping of epigenetic features and 3D chromatin structure via ViCAR - Genome Biology Methods to measure chromatin contacts at genomic regions bound by histone modifications or proteins are important tools to investigate chromatin organization. However, such methods do not capture the ...

For the first part of this journey, don't forget to check out genomebiology.biomedcentral.com/articles/10.... to find out how we developed a technique, ViCAR, for mapping 3D interactions specific to #epigenetic features (such as G4s)... 7/9

How do G4s function at enhancers? In our #proteomics pulldowns, RNA polymerase II subunits were enriched, together with known G4 binding proteins - but not some common architectural factors (e.g. YY1, CTCF) - we confirmed that some RNAPII subunits specifically bind G4s (Fig. 4A, F). 6/9

Inserting an unrelated G4 structure (Pu27 from the #Myc promoter - as featured in @isabelesain.bsky.social's brilliant work www.pnas.org/doi/abs/10.1...) recovers original globin expression and enhancer function (Figure 3D) 5/9

For the beta HS2 enhancer, this effect is masked by hyper activation of the neighbouring enhancer, HS3 - removing HS3 unveils a similar effect (Figure 3A-D for alpha, Figure 3E-H for beta). 4/9

We found a G4 in HS-40, the dominant enhancer of the alpha-globin locus regulatory region, replaced it with a sequence that can no longer form a G4; cognate gene expression, chromatin accessibility, and enhancer-promoter contacts were reduced. We then introduced a different G4-forming sequence - enhancer activity was restored.

What happened? In the alpha HS-40 enhancer, such a mutation (seven G-to-T mutations) was sufficient to reduce globin gene expression to levels observed when the whole enhancer region (of around 350 bases) is deleted. Enhancer-promoter contacts and local #chromatin accessibility is also reduced. 3/9

Using the classic #globin #superenhancer systems, we discovered two G4 structures in dominant enhancers in both the alpha globin and beta globin locus control systems - and replaced them with non-G4-forming sequences using CRISPR. 2/9

DNA G-quadruplex structures act as functional elements in α- and β-globin enhancers - Genome Biology Background Enhancer elements interact with target genes at a distance to modulate their expression, but the molecular details of enhancer–promoter interaction are incompletely understood. G-quadruplex...

How does (local #DNA) structure affect (3D #genome) structure? Can mutating G4s abolish #enhancers key for #blood function?

In the second part of our explorations of #G4s in gene regulation, we show how abolishing G-quadruplex structures in the genome disrupts enhancers. 1/9
doi.org/10.1186/s130...

We heard about "Alternative DNA structures in enhancer-promoter communication" from @seanflynn.bsky.social from @uniofexeter.bsky.social #Epigenetics2025

@uniofexeternews.bsky.social

🚨 We’re Hiring!🚨

Passionate about cancer research? Join Madzia Crossley's team to investigate how R-loop dysregulation contributes to cancer.

We have two exciting opportunities:
Research Associate: jobs.cam.ac.uk/job/50675/
Senior Scientific Associate: jobs.cam.ac.uk/job/50689/

PhD Studentship: Investigating the causes and consequences of R-loop dysregulation in cancer - Cancer Research UK Cambridge Institute Supervisor: Dr Magdalena Crossley Department/location: Cancer Research UK Cambridge Institute (CRUK CI) Course start date: 1st October 2025 Overview Dr Magdalena Crossley wishes to recruit a PhD stude...

🚨 Fully funded #PhD opportunity! 🚨

Passionate about cancer research? Join Dr Madzia Crossley's team to investigate how R-loop dysregulation contributes to cancer.

📍 Cambridge, UK
💰 Fully funded
📅 Apply by 24 March 2025

www.cruk.cam.ac.uk/vacancies/ph...

A great opportunity to work on #epigenetics, #genetics and gene regulation in #neuroscience with an inspirational young PI - please share and apply!

Dr Isabel Esain Garcia receives Cancer Research UK Cambridge Institute 2024 PhD Thesis Prize

Congratulations to @isabelesain.bsky.social, who is awarded the 2024 CRUK Cambridge Institute PhD Thesis Prize.

In her doctoral research, Bel discovered a new molecular mechanism in cancer gene regulation opening up a new therapeutic window for cancer treatments.

www.cruk.cam.ac.uk/news/bel-esa...

A great #PhD opportunity for anyone interested in #epigenetics in #neurons and the broader context of #neuroscience - having worked with @seanflynn.bsky.social and Jack, they are brilliant choices for mentors!

Improved simultaneous mapping of epigenetic features and 3D chromatin structure via ViCAR - Genome Biology Methods to measure chromatin contacts at genomic regions bound by histone modifications or proteins are important tools to investigate chromatin organization. However, such methods do not capture the ...

…and in the meantime, for anyone who missed it, here’s one we did earlier on mapping #epigenetic features together with their 3D #genomic contacts with ViCAR: genomebiology.biomedcentral.com/articles/10....

Thank you @seanflynn.bsky.social - looking forward to sharing science (mostly #epigenetics, #G4, gene regulation and #chromatin) with everyone, especially great work from the Flynn Lab!