Project description:Differentially expressed genes in the skin tissue of newborn Hu sheep were screened using an Agilent gene chip and RT-PCR. Differential expression analysis revealed 3 groups of large waves and small waves; 1067, 2071, and 3879 differentially expressed genes; and 137 genes common to all 3 groups. Differentially expressed genes were classified using gene ontology. They were found to be mainly involved in cell differentiation, proliferation, apoptosis, growth, immune response, and ion transport. RT-PCR results of 4 differentially expressed genes were consistent with gene chip results. Combined with related literature, our results suggest that BMP7, MMP2, SNAI1, SFXN1, CDKNIC, MT3, and POU1F1 may have important effects on the formation of large-wave and small-wave hair follicles. The samples collected with three full-sib individual and they borned at two days, what's more they were from the same paternal, each pair of big wave and small wave individuals from the same female parent.
Project description:Glucose is an important regulator of pancreatic β-cell function. In addition to the acute stimulation of insulin secretion, glucose stimulates long-term adaptive changes in gene expression that can either promote or antagonize the proliferative potential and function of β-cells. The glucose-sensing transcription factor carbohydrate response element binding protein (ChREBP) has been shown to promote both β-cell proliferation and dysfunction; however, the molecular mechanisms underlying these pleiotropic effects of ChREBP and glucose are not well understood. Here, we have generated time-resolved profiles of enhancer and transcriptional activity in response to glucose in the INS-1E pancreatic β-cell line. Our data outline a biphasic response with a first wave during which metabolic genes are activated, and a second wave where cell cycle genes are induced and β-cell identity genes are repressed. We show that ChREBP directly activates first wave genes, whereas repression and activation of second wave genes by ChREBP is indirect. By integrating motif enrichment within late-regulated enhancers with expression profiles of the associated transcription factors, we identify multiple putative regulators of the second wave, including RAR-related orphan receptor (ROR) γ, which we demonstrate is a novel direct ChREBP target gene. Importantly, we show that RORγ activity is necessary for full glucose-induced proliferation of both INS-1E and primary rat β-cells. Genome-wide assesment of the transcriptional response to glucose in INS-1E β-cells using RNA- ChIP- and DNase-seq
Project description:Across the cell cycle, mitochondrial dynamics are regulated by a cycling wave of actin polymerization/depolymerization. In metaphase, this wave induces the assembly of actin comet tails on mitochondria that propel these organelles to drive spatial mixing,resulting in their equitable inheritance by daughter cells. In contrast, during interphasethe cycling actin wave promotes localized mitochondrial fission. Here, we identify the F-actin nucleator/elongator FMNL1 as a positive regulator of the wave. Depletion of FMNL1 ablates the actin wave, allowing us to assess the functional consequences in interphase cells. FMNL1-depleted cells exhibit decreased mitochondrial polarization, decreased mitochondrial oxygen consumption, and increased production of reactive oxygen species. Accompanying these changes is a loss of hetero-fusion of wave-fragmented mitochondria. Thus we propose that the interphase actin wave maintains mitochondrial homeostasis by promoting mitochondrial content mixing. Finally, we investigated the mechanistic basis for the observation that the wave drives mitochondrial motility in metaphase but mitochondrial fission in interphase. Our data indicate that when the force of actin polymerization is resisted by mitochondrial tethering to microtubules, fission results. In striking contrast, upon microtubule depolymerization actin wave-enveloped mitochondria in interphase cells display comet tail motility characteristic of metaphase cells, which are devoid of microtubule-mitochondria interactions, suggesting that microtubule tethering inhibits comet tail-driven motility.