Genome-wide identification of palmitate-regulated immediate early genes and target genes in pancreatic beta-cells reveals a central role of NF-κB

2012 ◽  
Vol 39 (6) ◽  
pp. 6781-6789 ◽  
Author(s):  
Hyung Jin Choi ◽  
Seungwoo Hwang ◽  
Se-Hee Lee ◽  
You Ri Lee ◽  
Jiyon Shin ◽  
...  
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Target Genes ◽  
Immediate Early Genes ◽  
Immediate Early ◽  
Early Genes ◽  
Genome Wide

The role of immediate early genes in the stabilization of long-term potentiation

1991 ◽  
Vol 5 (2-4) ◽  
pp. 297-314 ◽  
Author(s):  
Wickliffe C. Abraham ◽  
Michael Dragunow ◽  
Warren P. Tate
Keyword(s):  
Immediate Early Genes ◽  
Long Term Potentiation ◽  
Immediate Early ◽  
Early Genes ◽  
Term Potentiation

scholarly journals Engineering combinatorial and dynamic decoders using synthetic immediate-early genes

2019 ◽  
Author(s):  
Pavithran T. Ravindran ◽  
Maxwell Z. Wilson ◽  
Siddhartha G. Jena ◽  
Jared E. Toettcher
Keyword(s):  
Growth Factor ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Target Genes ◽  
Immediate Early Genes ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Specific Target ◽  
Early Genes

AbstractFor tissues to grow and function properly, cells must coordinate actions such as proliferation, differentiation and apoptosis. This coordination is achieved in part by the activation of intracellular signaling pathways that trigger the expression of context-specific target genes. While the function of these natural circuits has been actively studied, synthetic biology provides additional powerful tools for deconstructing, repurposing, and designing novel signal-decoding circuits. Here we report the construction of synthetic immediate-early genes (synIEGs), target genes of the Erk signaling pathway that implement complex, user-defined regulation and can be monitored through the use of live-cell biosensors to track transcription and translation. We demonstrate the power and flexibility of this approach by confirming Erk duration-sensing by the FOS immediate-early gene, elucidating how the BTG2 gene is regulated by transcriptional activation and translational repression after growth-factor stimulation, and by designing a synthetic immediate-early gene that responds with AND-gate logic to the combined presence of growth factor and DNA damage stimuli. Our work paves the way to defining the molecular circuits that link signaling pathways to specific target genes, highlighting an important role for post-transcriptional regulation in signal decoding that may be masked by analyses of RNA abundance alone.

Intestinal perfusion induces rapid activation of immediate-early genes in weaning rats

2001 ◽  
Vol 281 (4) ◽  
pp. R1274-R1282 ◽  
Author(s):  
Lan Jiang ◽  
Heather Lawsky ◽  
Relicardo M. Coloso ◽  
Mary A. Dudley ◽  
Ronaldo P. Ferraris
Keyword(s):  
Mrna Expression ◽  
Target Genes ◽  
De Novo ◽  
Immediate Early Genes ◽  
Regulatory Elements ◽  
Intestinal Perfusion ◽  
Immediate Early ◽  
Mrna Levels ◽  
Early Genes

C- fos and c- jun are immediate-early genes (IEGs) that are rapidly expressed after a variety of stimuli. Products of these genes subsequently bind to DNA regulatory elements of target genes to modulate their transcription. In rat small intestine, IEG mRNA expression increases dramatically after refeeding following a 48-h fast. We used an in vivo intestinal perfusion model to test the hypothesis that metabolism of absorbed nutrients stimulates the expression of IEGs. Compared with those of unperfused intestines, IEG mRNA levels increased up to 11 times after intestinal perfusion for 0.3–4 h with Ringer solutions containing high (100 mM) fructose (HF), glucose (HG), or mannitol (HM). Abundance of mRNA returned to preperfusion levels after 8 h. Levels of c- fos and c- jun mRNA and proteins were modest and evenly distributed among enterocytes lining the villi of unperfused intestines. HF and HM perfusion markedly enhanced IEG mRNA expression along the entire villus axis. The perfusion-induced increase in IEG expression was inhibited by actinomycin-D. Luminal perfusion induces transient but dramatic increases in c- fos and c- jun expression in villus enterocytes. Induction does not require metabolizable or absorbable nutrients but may involve de novo gene transcription in cells along the villus.

Abstract 2318: The Type 2 Diabetes Gene CDKAL1 Discovered by Genome-wide Association is Expressed in Beta Cells and Modulated by Glucose Concentration

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Valgerdur Steinthorsdottir ◽  
Inga Reynisdottir ◽  
Gudmar Thorleifsson ◽  
Shyamali Ghosh ◽  
Rafn Benediktsson ◽  
...  
Keyword(s):  
Beta Cells ◽  
Glucose Concentration ◽  
Pancreatic Beta Cells ◽  
Pancreatic Beta Cell ◽  
Genome Wide Association ◽  
Neuronal Tissue ◽  
Genome Wide ◽  
Beta Cell Line

In our genome wide association study on type 2 diabetes (T2D), a variant we had previously identified in TCF7L2 stood out as the most significant finding. In addition, a variant of the CDKAL1 gene was found to be associated with increased risk of T2D in a nearly recessive manner, with genotype odds ratio for the homozygous carrier 1.45 and 1.55 for individuals of European and Asian ancestry respectively. The function of the CDKAL1 gene product is unknown but it is similar to another protein, CDK5RAP1, an inhibitor of the CDK5/p35 complex in neuronal tissue. This complex is also expressed in pancreatic beta cells and, in the presence of its active form, insulin expression is decreased under glucotoxic conditions. This led to the suggestion that CDKAL1 may be an inhibitor of the CDK5/p35 complex in beta cells, similar to the role of CDK5RAP1 in neuronal tissue. Furthermore, we have shown that the risk variant of CDKAL1 is associated with reduced insulin secretion and this effect is mostly seen for the homozygote where a 24% reduction in insulin response is observed compared to the heterozygous carriers or non-carriers. This is in line with the nearly recessive mode of inheritance observed for this variant with respect to disease risk. The aim of this study was to gain further insight into the functional role of CDKAL1 using the rat pancreatic beta cell line INS-1. The rat pancreatic beta cell line INS-1 was cultured in the presence of variable glucose concentration, ranging from 2.5–30 mM, to evaluate whether CDKAL1 expression is regulated by glucose concentration. We demonstrated that the expression of CDKAL1 in rat INS-1 cells varied according to glucose concentration in the culture medium with reduced expression detected under glucotoxic conditions compared to normal glucose concentration. This indicates that CDKAL1 expression in pancreatic beta cells is sensitive to glucose concentration. It is possible that this response to glucose may be affected in individuals carrying the variant of CDKAL1 that is associated to T2D. This could explain the reduced insulin secretion observed for these individuals in response to an oral glucose tolerance test.

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