Early-life epigenetic changes along the corticotropin-releasing hormone (CRH) gene influence resilience or vulnerability to heat stress later in life

Cramer, Tomer; Rosenberg, Tali; Kisliouk, Tatiana; Meiri, Noam

doi:10.1038/s41380-018-0280-5

Cited by 42 publications

(37 citation statements)

References 63 publications

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“…There was no sample size calculation. Nevertheless, the sample size was determined on the basis of previous studies (Kisliouk et al, 2017;Cramer et al, 2018). Sample number (n) included the number of individual chicks in each treatment group (indicated in Figure Legends).…”

Section: Quantification and Statistical Analysismentioning

confidence: 99%

“…These embryonic or early life environmental influences can lead to different stress responses, including vulnerability or resilience. Since these environmental effects are long-lasting, epigenetic regulatory mechanisms are probably involved and are key factors in the establishment and tuning of adult stress responses (Klengel and Binder, 2015;Turecki and Meaney, 2016;Horowitz, 2017;Cramer et al, 2018). The acquired stress response can have a broader impact than merely an adjusted response to the encountered stressor; it can also have a cross effect with other stress occurrences.…”

Section: Introductionmentioning

confidence: 99%

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Embryonic Heat Conditioning Induces TET-Dependent Cross-Tolerance to Hypothalamic Inflammation Later in Life

et al. 2020

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Early life encounters with stress can lead to long-lasting beneficial alterations in the response to various stressors, known as cross-tolerance. Embryonic heat conditioning (EHC) of chicks was previously shown to mediate resilience to heat stress later in life. Here we demonstrate that EHC can induce cross-tolerance with the immune system, attenuating hypothalamic inflammation. Inflammation in EHC chicks was manifested, following lipopolysaccharide (LPS) challenge on day 10 post-hatch, by reduced febrile response and reduced expression of LITAF and NFκB compared to controls, as well as nuclear localization and activation of NFκB in the hypothalamus. Since the crosstolerance effect was long-lasting, we assumed that epigenetic mechanisms are involved. We focused on the role of ten-eleven translocation (TET) family enzymes, which are the mediators of active CpG demethylation. Here, TET transcription during early life stress was found to be necessary for stress resilience later in life. The expression of the TET family enzymes in the midbrain during conditioning increased in parallel to an elevation in concentration of their cofactor α-ketoglutarate. In-ovo inhibition of TET activity during EHC, by the α-ketoglutarate inhibitor bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide (BPTES), resulted in reduced total and locus specific CpG demethylation in 10-day-old chicks and reversed both thermal and inflammatory resilience. In addition, EHC attenuated the elevation in expression of the stress markers HSP70, CRHR1, and CRHR2, during heat challenge on day 10 post-hatch. This reduction in expression was reversed by BPTES. Similarly, the EHC-dependent reduction of inflammatory gene expression during LPS challenge was eliminated in BPTES-treated chicks. Thus, TET family enzymes and CpG demethylation are essential for the embryonic induction of stress cross-tolerance in the hypothalamus.

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Section: Quantification and Statistical Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Embryonic Heat Conditioning Induces TET-Dependent Cross-Tolerance to Hypothalamic Inflammation Later in Life

et al. 2020

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“…Here, we analyzed the effects of temperature stress on different epigenetic modifications by comparing global DNA methylation and histone H4 acetylation, as well as the expression pattern of genes encoding various HDACs, HATs, DNMTs and TETs. Altered methylation in genes for heat shock proteins (HSPs) and corticotropinreleasing hormone, induced by heat stress during early embryonic stages, has an impact on the thermotolerance capacity in the postnatal life of broiler chickens [12,13]. We showed that, upon heat stress, C2C12 cells exhibited differential global DNA methylation compared to cells exposed to cold stress.…”

Section: Discussionmentioning

confidence: 99%

“…Genome-wide DNA methylation patterns are altered in the skeletal muscle of heat-stressed pigs [11]. Heat stress in postnatal stage (thermal conditioning) induces DNA methylation changes in the hypothalamicpituitary-adrenal axis which is involved in adaptation to heat load in adult chickens [12,13]. Key energy metabolites such as S-adenosylmethionine, acetyl CoA and ATP are essential for epigenetic modifications including DNA methylation and histone tail acetylation.…”

Section: Introductionmentioning

confidence: 99%

Cross-talk between energy metabolism and epigenetics during temperature stress response in C2C12 myoblasts

Sajjanar

Siengdee

Trakooljul

et al. 2019

International Journal of Hyperthermia

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Objective: Environmental stress induces disturbances in cell energy metabolism and may cause epigenetic modifications. This study aimed to understand the possible impact of temperature stress (35 C, 39 C and 41 C, compared to control 37 C) on energy metabolism and epigenetic modifications, such as DNA methylation and histone H4 acetylation, as well as its effects on the expression of genes responsible for epigenetic changes, in mouse skeletal myoblasts (C2C12 cells). Methods: The results showed significantly reduced maximal respiration and spare respiratory capacity under heat stress (39 C and 41 C), suggesting that mitochondrial functions were compromised under these conditions. The glycolytic capacity and glycolysis markedly increased following low-temperature stress (35 C). The results suggested that, under cold stress, cells prefer glycolysis as a rapid compensatory mechanism to meet energy requirements for adaptive thermogenic response. Results: Epigenetic changes (histone H4 acetylation and global DNA methylation) were observed under both heat and cold stress. Among the genes coding for DNA methyltransferases, the Dnmt3a was significantly increased under high-temperature conditions (39 C and 41 C), while Dnmt1 expression was significantly increased at low temperature (35 C), indicating that under these conditions the cells preferred maintenance of methylation to de novo methylation activity. An expression pattern similar to Dnmt3a was observed for Gcn5, encoding for a histone acetyltransferase. The study revealed that temperature stress induced changes in the metabolic profiles, as well as epigenetic modifications, including the dynamics of the key enzymes. Conclusion: The results indicated the existence of crosstalk mechanisms between energy metabolism and epigenetics during cell stress response. ARTICLE HISTORY

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“…Previous studies have shown that TET3 forms a protein-protein complex with REST to cooperatively function in the mouse retina (Perera et al, 2015) and hypothalamus (Cramer et al, 2019). To explore the relationship between TET3 and REST in the MOE, we first detected the expression of REST in the miR-200b/a KD and miR-200b/a + TET3 DKD mouse MOE.…”

Section: Tet3 Cooperation With Rest Is Critical For Gbc Proliferationmentioning

confidence: 99%

The micro RNA / TET 3/ REST axis is required for olfactory globose basal cell proliferation and male behavior

Yang

Zhou

et al. 2020

EMBO Reports

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In the main olfactory epithelium (MOE), new olfactory sensory neurons (OSNs) are persistently generated to replace lost neurons throughout an organism's lifespan. This process predominantly depends on the proliferation of globose basal cells (GBCs), the actively dividing stem cells in the MOE. Here, by using CRISPR/Cas9 and RNAi coupled with adeno‐associated virus (AAV) nose delivery approaches, we demonstrated that knockdown of miR‐200b/a in the MOE resulted in supernumerary Mash1‐marked GBCs and decreased numbers of differentiated OSNs, accompanied by abrogation of male behaviors. We further showed that in the MOE, miR‐200b/a targets the ten‐eleven translocation methylcytosine dioxygenase TET3, which cooperates with RE1‐silencing transcription factor (REST) to exert their functions. Deficiencies including proliferation, differentiation, and behaviors illustrated in miR‐200b/a knockdown mice were rescued by suppressing either TET3 or REST. Our work describes a mechanism of coordination of GBC proliferation and differentiation in the MOE and olfactory male behaviors through miR‐200/TET3/REST signaling.

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Early-life epigenetic changes along the corticotropin-releasing hormone (CRH) gene influence resilience or vulnerability to heat stress later in life

Cited by 42 publications

References 63 publications

Embryonic Heat Conditioning Induces TET-Dependent Cross-Tolerance to Hypothalamic Inflammation Later in Life

Embryonic Heat Conditioning Induces TET-Dependent Cross-Tolerance to Hypothalamic Inflammation Later in Life

Cross-talk between energy metabolism and epigenetics during temperature stress response in C2C12 myoblasts

The micro RNA / TET 3/ REST axis is required for olfactory globose basal cell proliferation and male behavior

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