2020
Hepatic TET3 contributes to type-2 diabetes by inducing the HNF4α fetal isoform
Da Li, Cao T, Sun X, Jin S, Di Xie, Huang X, Yang X, Carmichael GG, Taylor HS, Diano S, Huang Y. Hepatic TET3 contributes to type-2 diabetes by inducing the HNF4α fetal isoform. Nature Communications 2020, 11: 342. PMID: 31953394, PMCID: PMC6969024, DOI: 10.1038/s41467-019-14185-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDiabetes Mellitus, Type 2DioxygenasesDisease Models, AnimalDNA DemethylationDNA MethylationDNA-Binding ProteinsFastingGene Expression RegulationGlucagonGlucoseHepatocyte Nuclear Factor 3-betaHepatocyte Nuclear Factor 4LiverMaleMiceMice, Inbred C57BLMice, KnockoutPromoter Regions, GeneticProtein IsoformsTranscriptional ActivationTranscriptomeUp-RegulationConceptsHepatic glucose productionType 2 diabetesGlucose homeostasisAdult liverSystemic glucose homeostasisPotential therapeutic targetGenetic mouse modelsFetal versionKey gluconeogenic genesMouse modelTherapeutic targetHNF4α functionGlucose productionFetal isoformsLiverT2D.DiabetesPromoter demethylationGluconeogenic genesTET3 overexpressionHNF4αHomeostasisTET3Regulatory mechanismsIsoforms
2019
H19 lncRNA identified as a master regulator of genes that drive uterine leiomyomas
Cao T, Jiang Y, Wang Z, Zhang N, Al-Hendy A, Mamillapalli R, Kallen AN, Kodaman P, Taylor HS, Li D, Huang Y. H19 lncRNA identified as a master regulator of genes that drive uterine leiomyomas. Oncogene 2019, 38: 5356-5366. PMID: 31089260, PMCID: PMC6755985, DOI: 10.1038/s41388-019-0808-4.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsKey pathway genesGenome-scale studiesGenome-wide transcriptomeExtracellular matrixMethylation profiling analysisRegulation of expressionKey driver genesH19 single nucleotide polymorphismsEpigenetic modificationsMaster regulatorPathway genesTET expressionExpression changesExpression of H19H19 lncRNADriver genesProfiling analysisGenesH19Smooth muscle cellsUnifying mechanismMuscle cellsNovel target therapiesLncRNAs
2018
Elevated hepatic expression of H19 long noncoding RNA contributes to diabetic hyperglycemia
Zhang N, Geng T, Wang Z, Zhang R, Cao T, Camporez JP, Cai SY, Liu Y, Dandolo L, Shulman GI, Carmichael GG, Taylor HS, Huang Y. Elevated hepatic expression of H19 long noncoding RNA contributes to diabetic hyperglycemia. JCI Insight 2018, 3: e120304. PMID: 29769440, PMCID: PMC6012507, DOI: 10.1172/jci.insight.120304.Peer-Reviewed Original ResearchConceptsHepatic glucose productionGenome-wide methylationExpression of Hnf4aGluconeogenic transcription factorsDiabetic hyperglycemiaH19 depletionTranscriptome analysisTranscription factorsExpression of H19Molecular mechanismsDiet-induced diabetic miceExcessive hepatic glucose productionType 2 diabetesInsulin-dependent suppressionElevated hepatic expressionH19 knockdownH19Promoter methylationMechanistic explanationMethylationDiabetic patientsRNADiabetic miceInsulin resistanceH19 overexpression
2015
H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase
Zhou J, Yang L, Zhong T, Mueller M, Men Y, Zhang N, Xie J, Giang K, Chung H, Sun X, Lu L, Carmichael GG, Taylor HS, Huang Y. H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase. Nature Communications 2015, 6: 10221. PMID: 26687445, PMCID: PMC4703905, DOI: 10.1038/ncomms10221.Peer-Reviewed Original ResearchConceptsS-adenosylhomocysteine hydrolaseCellular componentsDNA methylation genomeGenome-wide methylation profilingOnly mammalian enzymeNumerous gene lociS-adenosylhomocysteineMode of regulationDiverse cellular componentsMethylation genomeMammalian developmentMethylation dynamicsIgf2-H19Mammalian enzymeRegulatory circuitsDNA methylationDependent methyltransferasesMethylation changesMethylation profilingPotent feedback inhibitorEpigenetic alterationsGene locusH19 lncRNAFeedback inhibitorS-adenosylmethionine