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:Actin-based protrusions driving cell migration are reinforced through positive feedback, but it is unclear how the cell restricts the eventual size of protrusions, or limits positive signals to allow them to split or retract. We have identified an evolutionarily conserved regulator of the protrusion machinery, which we name CYRI (CYFIP-related Rac interactor). CYRI binds specifically to activated Rac1 via a common motif that is also found in CYFIP, the Domain of Unknown Function DUF1394; we demonstrate that DUF1394 as a new class of Rac1 binding module. CYRI-depleted cells have broad, Scar/WAVE-enriched lamellipodia and display an enhanced duration and extent of pseudopod extension in response to optogenetic Rac1 activation. Conversely, CYRI overexpression suppresses recruitment of active Scar/WAVE complex to the cell edge and results in short-lived, unproductive protrusions. CYRI dynamically inhibits Scar/WAVE induced actin to focus positive protrusion signals and regulate pseudopod complexity. It therefore behaves like a “local inhibitor” predicted and described in widely accepted mathematical models, but not previously identified in living cells. CYRI is important for processes requiring polarity and plasticity of protrusions, including directional chemotactic migration and polarization of epithelial cysts.