scholarly journals GR-mediated transcriptional regulation of m6A metabolic genes contributes to diet-induced fatty liver in hens

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yue Feng ◽  
Yanlin Li ◽  
Wenduo Jiang ◽  
Yun Hu ◽  
Yimin Jia ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Fatty Liver ◽  
Transcriptional Activation ◽  
Laying Hens ◽  
Gene Activation ◽  
High Energy ◽  
Lipogenic Genes ◽  
Low Protein ◽  
Metabolic Genes

Abstract Background Glucocorticoid receptor (GR) mediated corticosterone-induced fatty liver syndrome (FLS) in the chicken by transactivation of Fat mass and obesity associated gene (FTO), leading to demethylation of N6-methyladenosine (m6A) and post-transcriptional activation of lipogenic genes. Nutrition is considered the main cause of FLS in the modern poultry industry. Therefore, this study was aimed to investigate whether GR and m6A modification are involved in high-energy and low protein (HELP) diet-induced FLS in laying hens, and if true, what specific m6A sites of lipogenic genes are modified and how GR mediates m6A-dependent lipogenic gene activation in HELP diet-induced FLS in the chicken. Results Laying hens fed HELP diet exhibit excess (P < 0.05) lipid accumulation and lipogenic genes activation in the liver, which is associated with significantly increased (P < 0.05) GR expression that coincided with global m6A demethylation. Concurrently, the m6A demethylase FTO is upregulated (P < 0.05), whereas the m6A reader YTHDF2 is downregulated (P < 0.05) in the liver of FLS chickens. Further analysis identifies site-specific demethylation (P < 0.05) of m6A in the mRNA of lipogenic genes, including FASN, SREBP1 and SCD. Moreover, GR binding to the promoter of FTO gene is highly enriched (P < 0.05), while GR binding to the promoter of YTHDF2 gene is diminished (P < 0.05). Conclusions These results implicate a possible role of GR-mediated transcriptional regulation of m6A metabolic genes on m6A-depenent post-transcriptional activation of lipogenic genes and shed new light in the molecular mechanism of FLS etiology in the chicken.

scholarly journals Low protein and high-energy diet: a possible natural cause of fatty liver hemorrhagic syndrome in caged White Leghorn laying hens

2016 ◽  
Vol 95 (3) ◽  
pp. 612-621 ◽  
Author(s):  
I. Rozenboim ◽  
J. Mahato ◽  
N.A. Cohen ◽  
O. Tirosh
Keyword(s):  
Fatty Liver ◽  
Laying Hens ◽  
High Energy ◽  
White Leghorn ◽  
Low Protein

scholarly journals Evidence for a Bigenic Chromatin Subdomain in Regulation of the Fetal-to-Adult Hemoglobin Switch

2008 ◽  
Vol 29 (6) ◽  
pp. 1635-1648 ◽  
Author(s):  
Hugues Beauchemin ◽  
Marie Trudel
Keyword(s):  
Transcriptional Activation ◽  
Gene Activation ◽  
Dna Demethylation ◽  
Open Chromatin ◽  
Chromosome Conformation ◽  
Hemoglobin Switching ◽  
Switching Patterns ◽  
Adult Hemoglobin ◽  
Globin Promoter

ABSTRACT During development, human β-globin locus regulation undergoes two critical switches, the embryonic-to-fetal and fetal-to-adult hemoglobin switches. To define the role of the fetal Aγ-globin promoter in switching, human β-globin-YAC transgenic mice were produced with the Aγ-globin promoter replaced by the erythroid porphobilinogen deaminase (PBGD) promoter (PBGDAγ-YAC). Activation of the stage-independent PBGDAγ-globin strikingly stimulated native Gγ-globin expression at the fetal and adult stages, identifying a fetal gene pair or bigenic cooperative mechanism. This impaired fetal silencing severely suppressed both δ- and β-globin expression in PBGDAγ-YAC mice from fetal to neonatal stages and altered kinetics and delayed switching of adult β-globin. This regulation evokes the two human globin switching patterns in the mouse. Both patterns of DNA demethylation and chromatin immunoprecipitation analysis correlated with gene activation and open chromatin. Locus control region (LCR) interactions detected by chromosome conformation capture revealed distinct spatial fetal and adult LCR bigenic subdomains. Since both intact fetal promoters are critical regulators of fetal silencing at the adult stage, we concluded that fetal genes are controlled as a bigenic subdomain rather than a gene-autonomous mechanism. Our study also provides evidence for LCR complex interaction with spatial fetal or adult bigenic functional subdomains as a niche for transcriptional activation and hemoglobin switching.

FGF21 prevents low protein diet-induced renal inflammation in aged mice

2021 ◽  
Author(s):  
Han Fang ◽  
Sujoy Ghosh ◽  
Landon Sims ◽  
Kirsten P. Stone ◽  
Cristal M Hill ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Renal Damage ◽  
Protective Role ◽  
Wild Type ◽  
Kidney Weight ◽  
Albumin Creatinine Ratio ◽  
Low Protein ◽  
The Impact ◽  
Protein Diets

Low protein diets extend lifespan through a comprehensive improvement in metabolic health across multiple tissues and organs. Many of these metabolic responses to protein restriction are secondary to transcriptional activation and release of FGF21 from the liver. However, the effects of a low protein (LP) diet on the kidney in the context of aging has not been examined. Therefore, the goal of the current study was to investigate the impact of chronic consumption of a LP diet on the kidney in aging mice lacking FGF21. Wild type (WT, C57BL/6J) and FGF21 KO mice were fed a normal protein (NP, 20% casein) or a LP (5% casein) diet ad libitum from 3 to19 months of age. The LP diet led to a decrease in kidney weight and urinary albumin/creatinine ratio in both WT and FGF21 KO mice. Although the LP diet produced only mild fibrosis and infiltration of leukocytes in WT kidneys, the effects were significantly exacerbated by the absence of FGF21. Accordingly, transcriptomic analysis showed that inflammation-related pathways were significantly enriched and upregulated in response to LP diet in FGF21 KO but not WT mice. Collectively, these data demonstrate that the LP diet negatively affected the kidney during aging, but in the absence of FGF21, the LP diet-induced renal damage and inflammation were significantly worse, indicating a protective role of FGF21 in the kidney.

Mechanisms of Transcriptional Regulation and Transformation by HOXA9

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. SCI-30-SCI-30
Author(s):  
Jay L. Hess ◽  
Cailin Collins ◽  
Joel Bronstein ◽  
Yuqing Sun ◽  
Surya Nagaraja
Keyword(s):  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Binding Sites ◽  
Target Genes ◽  
Conflicts Of Interest ◽  
Hematopoietic Stem ◽  
A Genome ◽  
The Impact

Abstract Abstract SCI-30 HOXA9 plays important roles in both development and hematopoiesis and is overexpressed in more than 50 percent of acute myeloid leukemias (AML). Nearly all cases of AML with mixed lineage leukemia (MLL) translocations show increased HOXA9 expression, as well as cases with mutation of the nucleophosmin gene NPM1, overexpression of CDX2, and fusions of NUP98. In most cases, upregulation of HOXA9 is accompanied by upregulation of its homeodomain-containing cofactor MEIS1, which directly interacts with HOXA9. While HOXA9 alone is sufficient for transformation of hematopoietic stem cells in culture, the addition of MEIS1 increases the transformation efficiency and results in rapidly fatal leukemias in transplanted animals. Despite the crucial role that HOXA9 plays in development, hematopoiesis, and leukemia, its transcriptional targets and mechanisms of action are poorly understood. We have used ChIP-seq to identify Hoxa9 and Meis1 binding sites on a genome-wide level in myeloblastic cells, profiled their associated epigenetic modifications, identified the target genes regulated by HOXA9 and identified HOXA9 interacting proteins. HOXA9 and MEIS1 cobind at hundreds of promoter distal, highly evolutionarily conserved sites showing high levels of histone H3K4 monomethylation and CBP/P300 binding. These include many proleukemogenic gene loci, such as Erg, Flt3, Myb, Lmo2, and Sox4. In addition, HOXA9 binding sites overlap a subset of enhancers previously implicated in myeloid differentiation and inflammation. HOXA9 binding at enhancers stabilizes association of MEIS1 and lineage-restricted transcription factors, including C/EBPα, PU.1, and STAT5A/B thereby promoting CBP/p300 recruitment, histone acetylation, and transcriptional activation. Current efforts are focused on using both biochemical and genetic approaches to assess the role of HOXA9 “enhanceosome” components C/EBPα, PU.1, and STAT5A/B in transcriptional regulation and leukemogenesis. Studies to date suggest that C/EBPα and PU.1 binding can occur in the absence of HOXA9/MEIS1, supporting a model in which these proteins act as pioneer transcription factors for establishment of poised, but not activated, HOXA9-regulated enhancers. Work is under way to assess the impact of high-level HOXA9 and MEIS1 on enhanceosome assembly and the role of recruitment of transcriptional coactivators involved in target gene up- or downregulation, including histone acetyltransferases and chromatin remodeling complexes. Collectively, our findings suggest that HOXA9-regulated enhancers are a fundamental mechanism of HOX-mediated transcription in normal development that is deregulated in leukemia. Disclosures: No relevant conflicts of interest to declare.

Analysis of the light regulatory mechanism in carotenoid production in Rhodosporidium toruloides NBRC 10032

2021 ◽  
Author(s):  
Khanh Dung Pham ◽  
Yuuki Hakozaki ◽  
Takeru Takamizawa ◽  
Atsushi Yamazaki ◽  
Harutake Yamazaki ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Oleaginous Yeast ◽  
Gene Activation ◽  
Light Response ◽  
Carotenoid Biosynthesis ◽  
Rhodosporidium Toruloides ◽  
End Joining ◽  
Carotenoid Production ◽  
Non Homologous End Joining

Abstract Light stimulates carotenoid production in an oleaginous yeast Rhodosporidium toruloides NBRC 10032 by promoting carotenoid biosynthesis genes. These genes undergo two-step of transcriptional activation. The potential light regulator, Cryptochrome DASH (CRY1), has been suggested to contribute to this mechanism. In this study, based on KU70 (a component of non-homologous end joining (NHEJ)) disrupting background, CRY1 disruptant was constructed to clarify CRY1 function. From analysis of CRY1 disruptant, it was suggested that CRY1 has the activation role of the carotenogenic gene expression. To obtain further insights into the light response, mutants varying carotenoid production were generated. Through analysis of mutants, the existence of the control two-step gene activation was proposed. In addition, our data analysis showed the strong possibility that R. toruloides NBRC 10032 is a homo-diploid strain.

scholarly journals Promoter Specificity and Biological Activity of Tethered AP-1 Dimers

2002 ◽  
Vol 22 (13) ◽  
pp. 4952-4964 ◽  
Author(s):  
Latifa Bakiri ◽  
Koichi Matsuo ◽  
Marta Wisniewska ◽  
Erwin F. Wagner ◽  
Moshe Yaniv
Keyword(s):  
Transcriptional Activation ◽  
Gene Activation ◽  
Dominant Negative ◽  
Activator Protein 1 ◽  
Loss Of Function ◽  
Single Chain ◽  
Promoter Specificity ◽  
Cycle Regulation ◽  
Nih 3T3

ABSTRACT Activator protein 1 (AP-1) is a group of dimeric transcription factors composed of Jun, Fos, and ATF family proteins. Both gain- and loss-of-function studies have revealed specific roles for individual AP-1 components in cell proliferation, differentiation, apoptosis, and other biological processes. However, little is known about the functions of specific AP-1 dimers. To test the importance of AP-1 composition in transcriptional activation, AP-1 monomers were joined via a flexible polypeptide tether to force specific pairing. The resultant single-chain AP-1 molecules showed DNA binding specificity and transcriptional activation potentials similar to those of untethered dimers, even in the presence of dominant-negative AP-1 monomers. c-Jun-containing dimers showed distinct promoter specificity in transient-transfection experiments, depending on the Fos, Fra, or ATF partner. When stably expressed in NIH 3T3 cells, c-Jun∼Fra2, but not c-Jun∼Fra1 and c-Jun∼cFos (the tilde indicates a tethered dimer), inhibited G0 arrest at confluency and under low-serum conditions and specifically activated cyclin A expression. These data suggest that the choice of dimerization partner defines the role of c-Jun in gene activation and cell cycle regulation and that single-chain AP-1 molecules provide a powerful tool for assessing the role of specific AP-1 dimers.

scholarly journals Serum Metabolomic Profiling to Reveal Potential Biomarkers for the Diagnosis of Fatty Liver Hemorrhagic Syndrome in Laying Hens

2021 ◽  
Vol 12 ◽  
Author(s):  
Lianying Guo ◽  
Jun Kuang ◽  
Yu Zhuang ◽  
Jialin Jiang ◽  
Yan Shi ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Clinical Diagnosis ◽  
Laying Hens ◽  
Roc Curves ◽  
High Energy ◽  
Flight Mass Spectrometry ◽  
Diagnostic Values ◽  
Potential Biomarkers ◽  
Tof Ms

Fatty liver hemorrhage syndrome (FLHS), a nutritional and metabolic disease that frequently occurs in laying hens, causes serious losses to the poultry industry. Nowadays, the traditional clinical diagnosis of FLHS still has its limitations. Therefore, searching for some metabolic biomarkers and elucidating the metabolic pathway in vivo are useful for the diagnosis and prevention of FLHS. In the present study, a model of FLHS in laying hens induced by feeding a high-energy, low-protein diet was established. Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) was used to analyze the metabolites in serum at days 40 and 80. The result showed that, in total, 40 differential metabolites closely related to the occurrence and development of FLHS were screened and identified, which were mainly associated with lipid metabolism, amino acid metabolism, and energy metabolism pathway disorders. Further investigation of differential metabolites showed 10 potential biomarkers such as 3-hydroxybutyric acid, oleic acid, palmitoleic acid, and glutamate were possessed of high diagnostic values by analyzing receiver operating characteristic (ROC) curves. In conclusion, this study showed that the metabolomic method based on GC-TOF-MS can be used in the clinical diagnosis of FLHS in laying hens and provide potential biomarkers for early risk evaluation of FLHS and further insights into FLHS development.

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