What are the molecular effects of a single drug exposure 💉 on reward system #dopamine neurons 🧠? We found an unexpected role of 3D genome 🧬 structure in long-term cellular memory of a single #cocaine exposure. @domSzabo @vedranfranke @WarrenWinick @apombo1 @BIMSB_MDC 1/6

@eleanorjpaul @batxes @samdemharter @lunazere9 @JPLopezAtalaya @MarioNicodemi @AltunaAkalin @KhodosevichLab @MarkU65668 Simona Bianco, Mykahilo Batiuk, Alexander Kukalev, Ulrich Pfisterer, Andrea Chiariello. Thanks to our funders 💰 for supporting the work @BIMSB_MDC @MDC_Berlin @helmholtz_de @4DNucleome @FEBSnews @neurocureberlin @dfg_public @novonordiskfond @LFINetwork @DonnellyCentre

This has been a fantastic collaboration involving people across countries 🇩🇪🇬🇧🇩🇰🇮🇹🇨🇦🇪🇸, continents 🌍 🌎 and fields of expertise 🐭💉🧬🔬🖥️. Many thanks to @eleanorjpaul @batxes @samdemharter @lunazere9 @JPLopezAtalaya @MarioNicodemi @AltunaAkalin @khodosevichLab @MarkU65668

Rbfox1 and many other genes with changes in 3D genome structure are most highly expressed in a DN sub-type of the medial VTA, known to project to secondary addiction regions. Our work suggests that these cells may be especially sensitive to the first cocaine exposure. 6/6

Chromatin decondensation occurs at many addiction genes, but the splicing factor gene Rbfox1 becomes most extensively unfolded only after 14 days! This progressive and long-lasting cascade of disruption could provide new insights into addiction inception and relapse. 5/6

We find that the cocaine-induced rewiring of 3D genome structure occurs at all scales of genome topology (TADs, loops, compartments, chromatin (de)condensation) consistently affecting cocaine-, addiction- and synaptic plasticity associated genes. 4/6

After a single cocaine exposure, we uncover massive reorganization of 3D genome structure in mouse midbrain dopaminergic neurons (DNs) which remarkably last or become worse after 2 weeks of abstinence, well beyond previously described transcriptional and synaptic effects. 3/6

Given the post-pandemic surge in global cocaine and poly-drug use, as well as the ongoing opioid crisis in North America, there is an urgent need to understand the effects of initial exposures to drugs of abuse and the inception of addiction. 2/6

Extensive folding variability between homologous chromosomes in mammalian cells https://t.co/7fHArXRQRo #bioRxiv

I am very pleased to share that our latest research🧑‍🔬 from @LabPombo, about allele-specific chromatin structure 🧬, now live on bioRxiv. Shout out to @apombo1, Alexander Kukalev, Rieke Kempfer and the rest of the team for this remarkable work of science. ↓ Short thread below ↓

What are the functional roles of 3D genome organization? Our paper in @Nature led by @_prashantbhat demonstrates how dynamic 3D genome organization around nuclear speckles plays a crucial role in regulating mRNA splicing efficiency. https://t.co/8KwfJHQWTt

🌱A huge thanks to the @Co_Biologists and to all the reviewers involved on planting our paper as a cherry blossom tree @For_Biologists 🌸 5/5

Splicing alterations precede gene expression events and morphological changes 4/5

Single-cell RNA-seq reveals heterogeneity of pluripotent states in Srm2 knockout stem cells 3/5

Srrm2-related gene expression changes are associated with embryo development processes and enriched in SRF targets 2/5

We show Srrm2 heterozygosity leads to loss of stemness and extensive gene expression changes 1/5

Our paper uncovering the role of SRRM2 splicing factor in stem cell pluripotency is published @BiologyOpen! 🚀 Huge joint effort coming from @LabPombo @BioComicsLab @Silviacamoeira @apombo1 @BIMSB_MDC @UCIBIO_Research @FCTNOVA https://t.co/dy0GsNpF86 ↓ Short thread below ↓

Incredibly excited that the DFG is establishing a priority programme in #neuroepigenetics. Initiative lead by Tanja Vogel with support from @BenschZimmer, André Fischer, @apombo1 and myself. Looking forward to great science to emerge from #EPIADAPT! https://t.co/woqcea3RgG

Thanks for the warm welcome these past weeks @QMULepigenetics! What an amazing community to be a part of 🤩🧬👨‍🔬👩‍💻

We're thrilled to share our latest paper on the role of Kdm1a preserving chromatin compartimentalization and gene silencing! You can check it in the link down below: 👇🏻 https://t.co/HXprfjgAoP Don’t miss it! @Beatriz_dBlanco @SergioNi92 #neuroepigenetics #Kdm1a 🧠