Browsing by Author "Gao, Fei"

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    B3 Transcription Factors Determine Iron Distribution and FERRITIN Gene Expression in Embryo but Do Not Control Total Seed Iron Content
    (2022) Grant-Grant, Susana; Schaffhauser, Macarena; Baeza-Gonzalez, Pablo; Gao, Fei; Conejero, Genevieve; Vidal, Elena A.; Gaymard, Frederic; Dubos, Christian; Curie, Catherine; Roschzttardtz, Hannetz
    Iron is an essential micronutrient for humans and other organisms. Its deficiency is one of the leading causes of anemia worldwide. The world health organization has proposed that an alternative to increasing iron content in food is through crop biofortification. One of the most consumed part of crops is the seed, however, little is known about how iron accumulation in seed occurs and how it is regulated. B3 transcription factors play a critical role in the accumulation of storage compounds such as proteins and lipids. Their role in seed maturation has been well characterized. However, their relevance in accumulation and distribution of micronutrients like iron remains unknown. In Arabidopsis thaliana and other plant models, three master regulators belonging to the B3 transcription factors family have been identified: FUSCA3 (FUS3), LEAFY COTYLEDON2 (LEC2), and ABSCISIC ACID INSENSITIVE 3 (ABI3). In this work, we studied how seed iron homeostasis is affected in B3 transcription factors mutants using histological and molecular approaches. We determined that iron distribution is modified in abi3, lec2, and fus3 embryo mutants. For abi3-6 and fus3-3 mutant embryos, iron was less accumulated in vacuoles of cells surrounding provasculature compared with wild type embryos. lec2-1 embryos showed no difference in the pattern of iron distribution in hypocotyl, but a dramatic decrease of iron was observed in cotyledons. Interestingly, for the three mutant genotypes, total iron content in dry mutant seeds showed no difference compared to wild type. At the molecular level, we showed that genes encoding the iron storage ferritins proteins are misregulated in mutant seeds. Altogether our results support a role of the B3 transcription factors ABI3, LEC2, and FUS3 in maintaining iron homeostasis in Arabidopsis embryos.
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    Super enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis
    (2021) Liu, Mengfei; Cao, Sheng; He, Li; Gao, Jinhang; Arab, Juan P.; Cui, Huarui; Xuan, Weixia; Gao, Yandong; Sehrawat, Tejasav S.; Hamdan, Feda H.; Ventura-Cots, Meritxell; Argemi, Josepmaria; Pomerantz, William C. K.; Johnsen, Steven A.; Lee, Jeong-Heon; Gao, Fei; Ordog, Tamas; Mathurin, Philippe; Revzin, Alexander; Bataller, Ramon; Yan, Huihuang; Shah, Vijay H.
    Alcoholic hepatitis (AH) is associated with liver neutrophil infiltration through activated cytokine pathways leading to elevated chemokine expression. Super-enhancers are expansive regulatory elements driving augmented gene expression. Here, we explore the mechanistic role of super-enhancers linking cytokine TNF alpha with chemokine amplification in AH. RNA-seq and histone modification ChIP-seq of human liver explants show upregulation of multiple CXCL chemokines in AH. Liver sinusoidal endothelial cells (LSEC) are identified as an important source of CXCL expression in human liver, regulated by TNF alpha /NF-kappa B signaling. A super-enhancer is identified for multiple CXCL genes by multiple approaches. dCas9-KRAB-mediated epigenome editing or pharmacologic inhibition of Bromodomain and Extraterminal (BET) proteins, transcriptional regulators vital to super-enhancer function, decreases chemokine expression in vitro and decreases neutrophil infiltration in murine models of AH. Our findings highlight the role of super-enhancer in propagating inflammatory signaling by inducing chemokine expression and the therapeutic potential of BET inhibition in AH treatment. Alcoholic hepatitis is characterized by intense liver inflammation driven by excessive cytokines and chemokines production and immune cell infiltration. Here the authors identify a super-enhancer that regulates the expression of multiple CXCL chemokines in alcoholic hepatitis and may be a potential therapeutic target.