BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis

Welz, Patrick-Simon; Zinna, Valentina M.; Symeonidi, Aikaterini; Koronowski, Kevin B.; Kinouchi, Kenichiro; Smith, Jacob G.; Guillén, I.; Castellanos, Andrés; Furrow, Stephen; Aragón, Ferrán; Crainiciuc, Georgiana; Prats, Neus; Caballero, Juan; Hidalgo, Andrés; Sassone–Corsi, Paolo; Benitah, Salvador Aznar

doi:10.1016/j.cell.2019.07.030

Cited by 41 publications

(65 citation statements)

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“…Surprisingly, liver‐RE mice retained BMAL1 binding to the majority of sites identified in WT mice, but only kept oscillation of 11% of BMAL1‐dependent transcripts and of 19% of hepatic cycling metabolites (Koronowski et al, ). Still, these results provided clear evidence that the liver clock retains an important degree of autonomy at the tissue level, paralleling findings obtained in similar studies investigating the epidermis clock (Welz et al, ).…”

Section: Liver Enhancer Dynamicssupporting

confidence: 87%

“…Up until recently, the degree of independence of the peripheral tissue clocks in respect to the SCN was not defined. To address this question, two recent studies have used BMAL1‐deficient mouse models with tissue‐specific reconstitution of this clock TF (RE mice; Koronowski et al, ; Welz et al, ). Surprisingly, liver‐RE mice retained BMAL1 binding to the majority of sites identified in WT mice, but only kept oscillation of 11% of BMAL1‐dependent transcripts and of 19% of hepatic cycling metabolites (Koronowski et al, ).…”

Section: Liver Enhancer Dynamicsmentioning

confidence: 99%

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Liver gene regulatory networks: Contributing factors to nonalcoholic fatty liver disease

Cebola

2020

WIREs Mechanisms of Disease

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Metabolic diseases such as nonalcoholic fatty liver disease (NAFLD) result from complex interactions between intrinsic and extrinsic factors, including genetics and exposure to obesogenic environments. These risk factors converge in aberrant gene expression patterns in the liver, which are underlined by altered cis‐regulatory networks. In homeostasis and in disease states, liver cis‐regulatory networks are established by coordinated action of liver‐enriched transcription factors (TFs), which define enhancer landscapes, activating broad gene programs with spatiotemporal resolution. Recent advances in DNA sequencing have dramatically expanded our ability to map active transcripts, enhancers and TF cistromes, and to define the 3D chromatin topology that contains these elements. Deployment of these technologies has allowed investigation of the molecular processes that regulate liver development and metabolic homeostasis. Moreover, genomic studies of NAFLD patients and NAFLD models have demonstrated that the liver undergoes pervasive regulatory rewiring in NAFLD, which is reflected by aberrant gene expression profiles. We have therefore achieved an unprecedented level of detail in the understanding of liver cis‐regulatory networks, particularly in physiological conditions. Future studies should aim to map active regulatory elements with added levels of resolution, addressing how the chromatin landscapes of different cell lineages contribute to and are altered in NAFLD and NAFLD‐associated metabolic states. Such efforts would provide additional clues into the molecular factors that trigger this disease. This article is categorized under: Biological Mechanisms > Metabolism Biological Mechanisms > Regulatory Biology Laboratory Methods and Technologies > Genetic/Genomic Methods

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Section: Liver Enhancer Dynamicssupporting

confidence: 87%

Section: Liver Enhancer Dynamicsmentioning

confidence: 99%

Liver gene regulatory networks: Contributing factors to nonalcoholic fatty liver disease

Cebola

2020

WIREs Mechanisms of Disease

View full text Add to dashboard Cite

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“…Some of these findings can be extrapolated to other peripheral tissues, including non-metabolically active organs, as demonstrated in the companion publication on the epidermis (Welz et al, 2019). The skin is the largest organ in the body and a huge sensory light receptor.…”

Section: Postulating a Bifid Model For Synchronization Of Peripheral mentioning

confidence: 89%

“…These studies revealed a series of metabolic pathways and metabolites that are able to oscillate autonomously from all other clocks, and constitute around 20% of the hepatic rhythms, including essential processes such as glycogen turnover and the NAD + salvage pathway. Importantly, this autonomous response of the liver clock was FIGURE 1 | Schematic representation of the main findings from the dual publication (Koronowski et al, 2019;Welz et al, 2019) commented. The mouse model reconstituting Bmal1 expression exclusively in the epidermis (Bmal1-RE mouse) or the liver (Liver-RE mouse) was generated from a conventional full-body Bmal1 knockout mouse (Bmal1-KO).…”

Section: Liver Circadian Clock Sets Its Own Pacementioning

confidence: 99%

“…Bmal knockout mice, in addition to loss of circadian rhythms, show characteristics of premature aging and a number of phenotypes including defective glucose homeostasis, calcification of joints and corneal degeneration (Kondratov et al, 2006). In back-to-back publications in Cell (Koronowski et al, 2019;Welz et al, 2019), the authors go one step further in transgenic engineering and generate a mouse model that reconstitutes Bmal1 expression in one particular organ, such as the epidermis (Bmal1-RE mouse) or the liver (Liver-RE mouse), with Bmal1 being completely absent in any other parts of the mouse body (Figure 1). This provides them with a valuable tool to dissect the unique contribution of peripheral tissues and organs to the master circadian mechanism, as well as to assess their degree of autonomy.…”

Section: Introductionmentioning

confidence: 99%

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“Defining the Independence of the Liver Circadian Clock” & “BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis”

Rotinen

2020

Front. Neurosci.

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Coupled network of the circadian clocks: a driving force of rhythmic physiology

2020

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The circadian system is composed of coupled endogenous oscillators that allow living beings, including humans, to anticipate and adapt to daily changes in their environment. In mammals, circadian clocks form a hierarchically organized network with a ‘master clock’ located in the suprachiasmatic nucleus of the hypothalamus, which ensures entrainment of subsidiary oscillators to environmental cycles. Robust rhythmicity of body clocks is indispensable for temporally coordinating organ functions, and the disruption or misalignment of circadian rhythms caused for instance by modern lifestyle is strongly associated with various widespread diseases. This review aims to provide a comprehensive overview of our current knowledge about the molecular architecture and system‐level organization of mammalian circadian oscillators. Furthermore, we discuss the regulatory roles of peripheral clocks for cell and organ physiology and their implication in the temporal coordination of metabolism in human health and disease. Finally, we summarize methods for assessing circadian rhythmicity in humans.

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BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis

Cited by 41 publications

References 0 publications

Liver gene regulatory networks: Contributing factors to nonalcoholic fatty liver disease

Liver gene regulatory networks: Contributing factors to nonalcoholic fatty liver disease

“Defining the Independence of the Liver Circadian Clock” & “BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis”

Coupled network of the circadian clocks: a driving force of rhythmic physiology

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