@RegGenomics

Professor of Molecular Biology. RNA, chromatin and transcriptional regulation.

 UCL, London
ucl.ac.uk/cancer/research/department-cancer-biology/regulatory-genomics-research-group
Joined May 2016
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Mutation of the basic patches within the loops completely abrogated PRC2 RNA binding activity. 5/8
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We also found that G4 RNA preferentially binds to the inactivated form of PRC2. SAM and coactivator peptides inhibit G4 RNA binding through an allosteric mechanism, which is prevented by a SAM binding mutation. 7/8
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Our data thus demonstrate that G4 RNA binds and inhibits a key chromatin modifier by engaging and repurposing two intrinsically disordered loops. 8/8
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John used cryo-EM to solve the structure of the monomeric PRC2 catalytic core bound to G4 RNA. He found that G4 RNA binds PRC2 through the disordered K and GR loops in EZH2. 3/8
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The flexible nature of these loops allows PRC2 to accommodate a range of G4 structures. 4/8
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Pleased to share our new pre-print revealing the mechanism through which G4 RNA binds and inhibits PRC2. Work led by John Houslay, a joint student between our group and the Wilson/Gamblin lab. 1/8 biorxiv.org/content/10.64898…
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G4 RNA was recently shown to inhibit PRC2 activity by inducing dimerisation, which occluded the active site. However, we found that the PRC2 catalytic core - G4 complex is mostly monomeric in physiological salt conditions. 2/8
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Karsten Rippe@KarstenRippeSep 9
🧬 How does HP1α repress, and what happens when transcription is induced? Our new paper in @MolecularCell: HP1α stays bound, its barrier is local, and mouse chromocenters switch nanodomain by nanodomain. Paper: doi.org/10.1016/j.molcel.202… Thread with figures: bsky.app/profile/karsten-rip…
Model scheme. Top, a silenced wild-type chromocenter with H3K9me3 nucleosomes and bound HP1α; VP16 is blocked, p65 and VPR activate it while HP1α and H3K9me3 stay. Bottom, a Suv39h dn chromocenter without HP1α, which p65 and VPR activate with acetylation and VP16 activates without it.

ALT Model scheme. Top, a silenced wild-type chromocenter with H3K9me3 nucleosomes and bound HP1α; VP16 is blocked, p65 and VPR activate it while HP1α and H3K9me3 stay. Bottom, a Suv39h dn chromocenter without HP1α, which p65 and VPR activate with acetylation and VP16 activates without it.

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Gabrijela Dumbović@Gabrijela_DSep 9
Incredibly happy to share the first publication from our lab, now published in Nature Cell Biology! 🎉 How do cells coordinate RNA processing with nuclear organization and the cell cycle? nature.com/articles/s41556-0… 1/10
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Igor Ulitsky@IgorUlitskyAug 24
One of the (well, >1) problems in the lncRNA field is that some of the lncRNAs are not real genes, i.e., do not represent a standalone locus that produces independent transcripts. Some cases are more 🤔 than others, e.g. lncDACH that Matt Bennet from @bakergroupcvs dove into 🧵
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LifeScienceAlliance@LSAjournalAug 3
This study identifies CpG islands at 3′UTRs as highly conserved, frequently methylated, and linked to cancer-related gene regulation. @Kanhere_Lab hubs.la/Q04qPckF0
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Molecular Cell@MolecularCellAug 5
Online Now: α-Satellite RNA maintains centromeric cohesion through R-loops dlvr.it/TTt08l
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Jonathan Henninger@jehenningerJun 8
Excited to share the first pre-print from our lab!! Check it out here! biorxiv.org/content/10.64898… We found that many RNA-binding proteins understood to regulate RNA processing can also function like transcription factors and cofactors to directly regulate transcription.
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UCL Cancer Institute@uclcancerMay 28
Independent Senior Research Fellow position available! Working between UCL and UCLH, you will apply machine learning to digital pathology data and electronic health records to drive new insights in cancer biology and improve patient care. To apply: lnkd.in/e9SX6WAT

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Does PRC2 interact with RNA or is it an artefact? See our preprint showing how stringent denaturing purifications with spike-in controls support direct interaction between PRC2 and RNA in cells. biorxiv.org/content/10.64898…
UV-crosslinked human cells containing Halo-tagged EZH2 were mixed with crosslinked mouse cells in which the protein was untagged and human EZH2 purified with Halo resin. Enrichment of human RNA (left) or mouse RNA (right) versus input was plotted against RNA abundance in the paired input sample. Windows with significant enrichment (p <10−6; binomial test) are shown in red. Human RNAs show enrichment versus input whereas mouse RNAs do not.

ALT UV-crosslinked human cells containing Halo-tagged EZH2 were mixed with crosslinked mouse cells in which the protein was untagged and human EZH2 purified with Halo resin. Enrichment of human RNA (left) or mouse RNA (right) versus input was plotted against RNA abundance in the paired input sample. Windows with significant enrichment (p <10−6; binomial test) are shown in red. Human RNAs show enrichment versus input whereas mouse RNAs do not.

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Igor Ulitsky@IgorUlitskyMay 15
Now out in @NatureBiotech ! Do lncRNAs commonly bind 1000s of genomic sites? Maybe they do, but the dozens of studies that report genomic binding maps of lncRNAs are deeply flawed, with probes binding suprious DNA sites rather than RNA-bound ones. nature.com/articles/s41587-0…

Widespread DNA off-targeting confounds RNA chromatin occupancy studies

Nature Biotechnology - Many long noncoding RNA–DNA binding peaks detected using common assays arise from technical artifacts.

nature.com
Igor Ulitsky@IgorUlitsky12 Nov 2025
A preprint‼️that's bound to ruffle some 🪶 "Widespread DNA off-targeting confounds studies of RNA chromatin occupancy" led by our @MicahGoldrich and Louis Delhaye from @pieter_mestdagh. TL;DR we show that many of lncRNA chromatin occupancy maps are flawed🧵biorxiv.org/content/10.1101/…

Widespread DNA off-targeting confounds studies of RNA chromatin occupancy

The importance of long noncoding RNA (lncRNA) functions is recognized across biological systems, but their modes of action remain poorly understood. One mechanism proposed to be particularly common...

biorxiv.org
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UCL Cancer Institute@uclcancerApr 22
Computational analysis is playing an ever increasing role in the detection, management and understanding of cancer. Equip yourself with the knowledge and skills to lead work in these areas with our new MSc in Computational Cancer, run with @UCLmedphys ucl.ac.uk/prospective-studen…
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Looking forward to hosting the next meeting of the London RNA Club on RNA Regulation in the Nucleus. Wednesday 25th March at UCL. Speakers including @BrockdorffLab, @Vichaico, @RobertVendramin and Folkert van Werven. eventleaf.com/e/LondonRNAClu… to register.
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Quezada Lab@QuezadaLabFeb 24
Come join our team!! linkedin.com/posts/quezada-l…

UCL – University College London | Quezada Lab

We are hiring! 🥼 We are searching for a passionate Antibody Engineering Research Technician to join our lab and support the development of next-generation biotherapeutics. 💉 If you have experience...

linkedin.com
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