Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, 0316 Oslo, Norway.
Department of Microbiology, Oslo University Hospital, 0372 Oslo, Norway.
Nucleic Acids Res. 2022 Feb 22;50(3):1351-1369. doi: 10.1093/nar/gkac027.
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.
调控脂肪组织形成和可塑性所需的基因表达网络的紧密控制对于适应能量需求和环境线索至关重要。然而，协调导致脂肪细胞分化的全局和巨大转录变化的机制仍有待充分阐明。我们使用 SLAMseq 和 ChIPseq 研究了脂肪细胞分化过程中 SUMO 修饰途径对新生转录的调控。我们发现，SUMO 修饰途径在分化中有双重功能；它支持前脂肪细胞特异性基因的初始下调，同时促进成熟脂肪细胞转录程序的建立。通过质谱法对分化中的脂肪细胞内源性 SUMO 组动态进行特征描述，我们发现 PPARγ/RXR 等特定转录因子及其共同因子的 SUMO 化与脂肪生成基因的转录有关。最后，我们以 RXR 为模型，发现 SUMO 化可能通过支持转录因子的染色质发生来调节脂肪生成转录。我们的数据表明，SUMO 修饰途径支持功能性脂肪细胞形成所需的转录网络的重新布线。本研究还为细胞分化和发育领域的科学家提供了脂肪细胞分化过程中 SUMO-染色质景观、SUMO 调控转录和内源性 SUMO 化位点动态的深入资源。
