Waves of sumoylation support transcription dynamics during adipocyte differentiation

Xu Zhao, Ivo A. Hendriks, Stephanie Le Gras, Tao Ye, Lucía Ramos-Alonso, Aurelie Nguea P, Guro Flor Lien, Fatemeh Ghasemi, Arne Klungland, Bernard Jost, Jorrit M. Enserink, Michael L. Nielsen, Pierre Chymkowitch*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

7 Citations (Scopus)
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Abstract

Tight control of gene expression networks required for adipose tissue formation and plasticity is essential for adaptation to energy needs and environmental cues. However, the mechanisms that orchestrate the global and dramatic transcriptional changes leading to adipocyte differentiation remain to be fully unraveled. We investigated the regulation of nascent transcription by the sumoylation pathway during adipocyte differentiation using SLAMseq and ChIPseq. We discovered that the sumoylation pathway has a dual function in differentiation; it supports the initial downregulation of pre-Adipocyte-specific genes, while it promotes the establishment of the mature adipocyte transcriptional program. By characterizing endogenous sumoylome dynamics in differentiating adipocytes by mass spectrometry, we found that sumoylation of specific transcription factors like PPARγ/RXR and their co-factors are associated with the transcription of adipogenic genes. Finally, using RXR as a model, we found that sumoylation may regulate adipogenic transcription by supporting the chromatin occurrence of transcription factors. Our data demonstrate that the sumoylation pathway supports the rewiring of transcriptional networks required for formation of functional adipocytes. This study also provides the scientists in the field of cellular differentiation and development with an in-depth resource of the dynamics of the SUMO-chromatin landscape, SUMO-regulated transcription and endogenous sumoylation sites during adipocyte differentiation.

Original languageEnglish
JournalNucleic Acids Research
Volume50
Issue number3
Pages (from-to)1351-1369
Number of pages19
ISSN0305-1048
DOIs
Publication statusPublished - 2022

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© 2022 The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.

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