Active transcription and epigenetic reactions synergistically regulate meso-scale genomic organization

Kant, Aayush; Guo, Zixian; Vinayak, Vinayak; Neguembor, Maria Victoria; Li, Wing Shun; Agrawal, Vasundhara; Pujadas, Emily; Almassalha, Luay; Backman, Vadim; Lakadamyali, Melike; Cosma, Maria Pia; Shenoy, Vivek B.

Active transcription and epigenetic reactions synergistically regulate meso-scale genomic organization

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dc.contributor.author Kant, Aayush
dc.contributor.author Guo, Zixian
dc.contributor.author Vinayak, Vinayak
dc.contributor.author Neguembor, Maria Victoria
dc.contributor.author Li, Wing Shun
dc.contributor.author Agrawal, Vasundhara
dc.contributor.author Pujadas, Emily
dc.contributor.author Almassalha, Luay
dc.contributor.author Backman, Vadim
dc.contributor.author Lakadamyali, Melike
dc.contributor.author Cosma, Maria Pia
dc.contributor.author Shenoy, Vivek B.
dc.date.accessioned 2024-09-06T06:14:22Z
dc.date.available 2024-09-06T06:14:22Z
dc.date.issued 2024
dc.description.abstract In interphase nuclei, chromatin forms dense domains of characteristic sizes, but the influence of transcription and histone modifications on domain size is not understood. We present a theoretical model exploring this relationship, considering chromatin-chromatin interactions, histone modifications, and chromatin extrusion. We predict that the size of heterochromatic domains is governed by a balance among the diffusive flux of methylated histones sustaining them and the acetylation reactions in the domains and the process of loop extrusion via supercoiling by RNAPII at their periphery, which contributes to size reduction. Super-resolution and nano-imaging of five distinct cell lines confirm the predictions indicating that the absence of transcription leads to larger heterochromatin domains. Furthermore, the model accurately reproduces the findings regarding how transcription-mediated supercoiling loss can mitigate the impacts of excessive cohesin loading. Our findings shed light on the role of transcription in genome organization, offering insights into chromatin dynamics and potential therapeutic targets.
dc.description.sponsorship This work was supported by NIH Award U54CA261694 (V.B.S.); NCI Awards R01CA232256 (V.B.S.); NSF CEMB Grant CMMI-154857 (V.B.S.); NSF Grants MRSEC/DMR-1720530 and DMS-1953572 (V.B.S.); NIBIB Awards R01EB017753 and R01EB030876 (V.B.S.). This work made use of the BioCryo facility of Northwestern University’s NUANCE Center, which has received support from the SHyNE Resource (NSF ECCS-2025633), the IIN, and Northwestern’s MRSEC program (NSF DMR-1720139). We acknowledge the support from NIH grants U54CA268084 (V.B.), R01CA228272 (V.B.), R01CA225002 (V.B.), NSF grant EFMA-1830961 (V.B.), and philanthropic support from Rob and Kristin Goldman (V.B.). We acknowledge the support from the European Union’s Horizon 2020 Research and Innovation Programme (no. 964342 to M.P.C.); Ministerio de Ciencia e Innovación (grant no. 008506-PID2020- 114080GB-I00 to M.P.C.; AGAUR grant from Secretaria d’Universitats i Recerca del Departament d’Empresa iConeixement de la Generalitat de Catalunya (grant no. 006712 BFU2017-86760-P (AEI/FEDER, UE) to M.P.C.).
dc.format.mimetype application/pdf
dc.identifier.citation Kant A, Guo Z, Vinayak V, Neguembor MV, Li WS, Agrawal V, et al. Active transcription and epigenetic reactions synergistically regulate meso-scale genomic organization. Nat Commun. 2024 May 21;15(1):4338. DOI: 10.1038/s41467-024-48698-z
dc.identifier.doi http://dx.doi.org/10.1038/s41467-024-48698-z
dc.identifier.issn 2041-1723
dc.identifier.uri http://hdl.handle.net/10230/61030
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Nat Commun. 2024 May 21;15(1):4338
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/964342
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-114080GB-I00
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-86760-P
dc.rights © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword Biological physics
dc.subject.keyword Computational biophysics
dc.subject.keyword Super-resolution microscopy
dc.title Active transcription and epigenetic reactions synergistically regulate meso-scale genomic organization
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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