Chronic cAMP activation induces adipocyte browning through discordant biphasic remodeling of transcriptome and chromatin accessibility

So, Jisun; Taleb, Solaema; Wann, Jamie; Strobel, Olivia; Kim, Kyungchan; Roh, Hyun Cheol

doi:10.1016/j.molmet.2022.101619

Cited by 5 publications

(5 citation statements)

References 77 publications

(101 reference statements)

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“…To assess the regulation of enhancers and promoters in contributing to tissue discrepancies in gene expression, we investigated TF binding in histone modification differential enhancers and promoters. The motifs of EBF1, ETS1, NFIL3 and ERG TFs, which were previously reported to regulate adipocyte development in vivo and promote energy metabolism for obesity (Flajollet et al, 2012;Hesslein et al, 2009;So et al, 2022;Zhang et al, 2016), were significantly enriched (p < 0.01) in adipose tissue enhancers, and these TFs were expressed in adipose tissue (Figure 3e,f). The IRF family is significantly enriched in adipose tissue promoters (Figure 3g,h), and it is a major transcriptional regulator of adipose inflammation (Friesen et al, 2017;Kumari et al, 2016).…”

Section: Transcriptional and Epigenetic Discrepancies Between CX Adip...mentioning

confidence: 71%

H3K27ac modification and transcription characteristics of adipose and muscle tissues in Chuxiang Black pig

Kuang,

Xu,

Zhou

et al. 2024

Animal Genetics

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The establishment of high‐quality pork breeds for improving meat quality in the pig industry is needed. The Chuxiang Black (CX) pig is a new breed developed from Chinese local pigs and Western lean pigs that has a high proportion of lean meat and excellent meat quality. However, the characteristics of cis‐regulatory elements in CX pigs are still unknown. In this study, cis‐regulatory elements of muscle and adipose tissues in CX pigs were investigated using ChIP‐seq and RNA sequencing. Compared with the reported cis‐regulatory elements of muscle and adipose tissues, 1768 and 1012 highly activated enhancers and 433 and 275 highly activated promoters in CX muscle and adipose tissues were identified, respectively. Motif analysis showed that transcription factors, such as MEF2A and MEF2C, were core regulators of highly activated enhancers and promoters in muscle. Similarly, the transcription factors JUNB and CUX1 were identified as essential for highly activated enhancers and promoters in CX adipose tissue. These results enrich the resources for the analysis of cis‐regulatory elements in the pig genome and provide new basic data for further meat quality improvement through breeding in pigs.

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Section: Transcriptional and Epigenetic Discrepancies Between CX Adip...mentioning

confidence: 71%

H3K27ac modification and transcription characteristics of adipose and muscle tissues in Chuxiang Black pig

Kuang,

Xu,

Zhou

et al. 2024

Animal Genetics

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“…Indeed, sustained adrenergic stimulation elicits a global downregulation of splicing factors' gene expression in the pathological context of pheochromocytoma ( 28 ). Interestingly, such transcriptional remodeling of the splicing machinery was not observed upon rosiglitazone-induced beiging, a discrepancy that likely results from inherently different transcriptomic responses elicited by PPARγ- and cAMP-induced adipocyte browning ( 44 ). Instead, we find that differential isoform expression upon rosiglitazone-induced beiging mostly results from alternative TSS usage, rather than from alternative splicing of downstream exons.…”

Section: Discussionmentioning

confidence: 99%

Alternative isoform expression of key thermogenic genes in human beige adipocytes

Hazell Pickering,

Abdelhalim,

Collas

et al. 2024

Front. Endocrinol.

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BackgroundThe beneficial effect of thermogenic adipocytes in maintaining body weight and protecting against metabolic disorders has raised interest in understanding the regulatory mechanisms defining white and beige adipocyte identity. Although alternative splicing has been shown to propagate adipose browning signals in mice, this has yet to be thoroughly investigated in human adipocytes.MethodsWe performed parallel white and beige adipogenic differentiation using primary adipose stem cells from 6 unrelated healthy subjects and assessed differential gene and isoform expression in mature adipocytes by RNA sequencing.ResultsWe find 777 exon junctions with robust differential usage between white and beige adipocytes in all 6 subjects, mapping to 562 genes. Importantly, only 10% of these differentially spliced genes are also differentially expressed, indicating that alternative splicing constitutes an additional layer of gene expression regulation during beige adipocyte differentiation. Functional classification of alternative isoforms points to a gain of function for key thermogenic transcription factors such as PPARG and CITED1, and enzymes such as PEMT, or LPIN1. We find that a large majority of the splice variants arise from differential TSS usage, with beige-specific TSSs being enriched for PPARγ and MED1 binding compared to white-specific TSSs. Finally, we validate beige specific isoform expression at the protein level for two thermogenic regulators, PPARγ and PEMT.DiscussionThese results suggest that differential isoform expression through alternative TSS usage is an important regulatory mechanism for human adipocyte thermogenic specification.

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“…Indeed, So et al (2022) first provided experimental evidence showing that protein encoded by NFIL3 was found to participate in adipose tissue thermogenesis, in vitro. The knockdown of NFIL3 disrupted the thermogenesis of systemic energy homeostasis in the adipocyte cell line of mice [75]. Thus, we postulated that the upregulation of these circadian rhythm-related genes may also increase cold resistance in the eel goby by acting on the cellular metabolism processes such as energy homeostasis, as well.…”

Section: Common Processes Involved In the Cold Stress Responsementioning

confidence: 91%

Comparative Transcriptome Analyses Provide New Insights into the Evolution of Divergent Thermal Resistance in Two Eel Gobies

Liu,

Liu

et al. 2023

CIMB

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Adaptation to thermal conditions in tidal mudflats always involves tolerating frequent fluctuations and often extreme environmental temperatures. Regulation of gene expression plays a fundamental role in the evolution of these thermal adaptations. To identify the key gene regulatory networks associated with the thermal adaptation, we investigated the capability of cold tolerance, as well as the transcriptomic changes under cold stress in two mudflat inhabitants (Odontamblyopus lacepedii and O. rebecca) with contrasting latitude affinity. Our results revealed a remarkable divergent capacity of cold tolerance (CTmin: 0.61 °C vs. 9.57 °C) between the two gobies. Analysis of transcriptomic changes under cold stress unveiled 193 differentially expressed genes exhibiting similar expression profiles across all tissues and species, including several classic metabolic and circadian rhythm molecules such as ACOD and CIART that may represent the core cold response machinery in eel gobies. Meanwhile, some genes show a unique expression spectrum in the more cold-tolerant O. lacepedii suggesting their roles in the enhanced cold tolerance and hence the extreme thermal adaptations. In addition, a weighted gene co-expression network analysis (WGCNA) revealed a subset of metabolic hub genes including MYH11 and LIPT2 showing distinct down-regulation in O. lacepedii when exposed to cold stress which highlights the role of reduced energy consumption in the enhanced cold tolerance of eel gobies. These findings not only provide new insights into how mudflat teleosts could cope with cold stress and their potential evolutionary strategies for adapting to their thermal environment, but also have important implications for sound management and conservation of their fishery resources in a scenario of global climate warming in the marine realm.

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Chronic cAMP activation induces adipocyte browning through discordant biphasic remodeling of transcriptome and chromatin accessibility

Cited by 5 publications

References 77 publications

H3K27ac modification and transcription characteristics of adipose and muscle tissues in Chuxiang Black pig

H3K27ac modification and transcription characteristics of adipose and muscle tissues in Chuxiang Black pig

Alternative isoform expression of key thermogenic genes in human beige adipocytes

Comparative Transcriptome Analyses Provide New Insights into the Evolution of Divergent Thermal Resistance in Two Eel Gobies

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