DNA-induced spatial entrapment of general transcription machinery can stabilize gene expression in a nondividing cell

Author:

Javed Khayam12,Jullien Jerome3,Agarwal Gaurav4,Lawrence Nicola12,Butler Richard1,Ioannou Pantelis Savvas1,Nazir Farhat5,Gurdon J. B.12ORCID

Affiliation:

1. Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom

2. Department of Zoology, University of Cambridge, Cambridge CB2 0EJ, United Kingdom

3. CRTI, INSERM, CHU Nantes, Nantes Université, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes F-44000, France

4. Medical Sciences Division, University of Oxford, Oxford OX1 2JD, United Kingdom

5. Abcam Plc, Cambridge CB2 0AX, United Kingdom

Abstract

Significance How differentiated cells such as muscle or nerve maintain their gene expression for prolonged times is currently elusive. Here, using Xenopus oocyte, we have shown that the stability of gene expression in nondividing cells may arise due to the local entrapment of transcriptional machinery to specific gene transcription start sites. We found that within the same nucleus active versus inactive versions of the same gene are spatially segregated through liquid–liquid phase separation. We further observe that silent genes are associated with RNA-Pol-II phosphorylated on Ser5 but fails to attract RNA-Pol-II elongation factors. We propose that liquid–liquid phase separation mediated entrapment of limiting transcriptional machinery factors maintain stable expression of some genes in nondividing cells.

Funder

Wellcome

Cancer Research UK

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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