RESUMO
Fatty acid and triglyceride synthesis increases greatly in response to feeding and insulin. This lipogenic induction involves coordinate transcriptional activation of various enzymes in lipogenic pathway, including fatty acid synthase and glycerol-3-phosphate acyltransferase. Here, we show that JMJD1C is a specific histone demethylase for lipogenic gene transcription in liver. In response to feeding/insulin, JMJD1C is phosphorylated at T505 by mTOR complex to allow direct interaction with USF-1 for recruitment to lipogenic promoter regions. Thus, by demethylating H3K9me2, JMJD1C alters chromatin accessibility to allow transcription. Consequently, JMJD1C promotes lipogenesis in vivo to increase hepatic and plasma triglyceride levels, showing its role in metabolic adaption for activation of the lipogenic program in response to feeding/insulin, and its contribution to development of hepatosteatosis resulting in insulin resistance.
Assuntos
Histona Desmetilases com o Domínio Jumonji/metabolismo , Lipogênese/fisiologia , Oxirredutases N-Desmetilantes/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Ingestão de Alimentos/genética , Ingestão de Alimentos/fisiologia , Feminino , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Células Hep G2 , Histonas/metabolismo , Humanos , Insulina/metabolismo , Insulina/farmacologia , Resistência à Insulina , Histona Desmetilases com o Domínio Jumonji/genética , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Lisina/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxirredutases N-Desmetilantes/genética , Fosforilação , Regiões Promotoras Genéticas , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Fatores Estimuladores Upstream/metabolismoRESUMO
The olfactory epithelium is a sensory neuroepithelium that supports adult neurogenesis and tissue regeneration following injury, making it an excellent model for investigating neural stem cell regulation in vivo. Previous studies have identified the horizontal basal cell (HBC) as the neural stem cell of the postnatal olfactory epithelium. However, the molecules and pathways regulating HBC self-renewal and differentiation are unknown. In the present study, we demonstrate that the transcription factor p63, a member of the p53 tumor suppressor gene family known to regulate stem cell dynamics in other epithelia, is highly enriched in HBCs. We show that p63 is required cell autonomously for olfactory stem cell renewal and further demonstrate that p63 functions to repress HBC differentiation. These results provide critical insight into the genetic regulation of the olfactory stem cell in vivo and more generally provide an entrée toward understanding the coordination of stem cell self-renewal and differentiation.
Assuntos
Diferenciação Celular/genética , Regulação da Expressão Gênica/genética , Neurogênese/genética , Bulbo Olfatório/citologia , Fosfoproteínas/metabolismo , Células-Tronco/fisiologia , Transativadores/metabolismo , Animais , Animais Recém-Nascidos , Proteínas de Bactérias/genética , Citometria de Fluxo , Perfilação da Expressão Gênica , Queratina-15 , Queratina-5/genética , Proteínas Luminescentes/genética , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Mucosa Olfatória/citologia , Análise de Sequência com Séries de Oligonucleotídeos , Fosfoproteínas/genética , Proteínas/genética , RNA não Traduzido , Transativadores/genéticaRESUMO
We use Arabidopsis thaliana embryogenesis as a model system for studying intercellular transport via plasmodesmata (PD). A forward genetic screen for altered PD transport identified increased size exclusion limit (ise) 1 and ise2 mutants with increased intercellular transport of fluorescent 10-kDa tracers. Both ise1 and ise2 exhibit increased formation of twinned and branched PD. ISE1 encodes a mitochondrial DEAD-box RNA helicase, whereas ISE2 encodes a DEVH-type RNA helicase. Here, we show that ISE2 foci are localized to the chloroplast stroma. Surprisingly, plastid development is defective in both ise1 and ise2 mutant embryos. In an effort to understand how RNA helicases that localize to different organelles have similar impacts on plastid and PD development/function, we performed whole-genome expression analyses. The most significantly affected class of transcripts in both mutants encode products that target to and enable plastid function. These results reinforce the importance of plastid-mitochondria-nucleus cross-talk, add PD as a critical player in the plant cell communication network, and thereby illuminate a previously undescribed signaling pathway dubbed organelle-nucleus-plasmodesmata signaling. Several genes with roles in cell wall synthesis and modification are also differentially expressed in both mutants, providing new targets for investigating PD development and function.