Expression profile of FLA2 (highest LSC frequency) and FLB1 (lowest LSC frequency) leukemias.
A role for GPx3 in activity of normal and leukemia stem cells.
Specimen part
View SamplesWe deleted Tfr1 in the heart to determine the role of Tfr1 in iron uptake in normal cardiac funciton We used microarrays to identify global gene changes associated with deletion of Tfr1 in skeletal muscle
Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart.
Age, Specimen part
View SamplesThe integration of positive and negative intra- and extra-cellular signals dictates whether a cell will proliferate or differentiate. While it is intuitive to speculate that nutrients availability may influence this alternative, a comprehensive complement of the molecular determinants involved in this process has not been elucidated yet. In this study, we will investigate how nutrients (glucose) affect skeletal myogenesis. C2C12 cells will be cultured in high glucose and low glucose conditions, and their differenciation will be studied.
Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt.
No sample metadata fields
View SamplesAffymetrix expression arrays were used to compare expression patterns upon knockdown of PARP-1, PARG, SIRT1, or macroH2A in comparison to Luciferase control.
Global analysis of transcriptional regulation by poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in MCF-7 human breast cancer cells.
No sample metadata fields
View SamplesPoly(ADP-ribose) polymerase-1 (PARP-1) and poly(ADP-ribose) glycohydrolase (PARG) are enzymes that modify target proteins in the nucleus by the addition and removal, respectively, of ADP-ribose polymers. Although a role for PARP-1 in gene regulation has been well established, the role of PARG is less clear. To investigate how PARP-1 and PARG coordinately regulate global patterns of gene expression, we used short hairpin RNAs (shRNAs) to stably knockdown PARP-1 or PARG in MCF-7 cells, followed by expression microarray analyses.
Global analysis of transcriptional regulation by poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in MCF-7 human breast cancer cells.
No sample metadata fields
View SamplesIn mammals, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 1 (NMNAT-1) constitute a nuclear NAD+ salvage pathway, regulating cellular functions of the NAD+-dependent deacetylase SIRT1. However, little is known about the molecular mechanisms by which NAD+ biosynthesis controls gene transcription in the nucleus. In this study, we show that stable knockdown of NAMPT or NMNAT-1 in MCF-7 breast cancer cells significantly reduced total cellular NAD+ levels. Expression microarray analyses demonstrate that both enzymes have broad and overlapping functions in gene regulation. SIRT1 is a key mediator of NAMPT- and NMNAT-1-dependent gene regulation, and is found at promoters of many of the target genes. Furthermore, SIRT1 deacetylase activity at these promoters is regulated by NAMPT and NMNAT-1. Most significantly, NMNAT-1 interacts with SIRT1 and is recruited to target gene promoters by SIRT1. Our results reveal an unexpected mechanism for the direct control of SIRT1 deacetylase activity at target gene promoters by NMNAT-1. Interactions between NMNAT-1 and SIRT1 at gene promoters may provide a platform for integration of multiple signaling pathways that regulate transcription.
Enzymes in the NAD+ salvage pathway regulate SIRT1 activity at target gene promoters.
No sample metadata fields
View SamplesSirtuins are a family of protein deacetylases, deacylases, and ADP-ribosyltransferases that regulate life span, control the onset of numerous age-associated diseases, and mediate metabolic homeostasis. We have uncovered a novel role for the mitochondrial sirtuin SIRT4 in the regulation of hepatic lipid metabolism during changes in nutrient availability. We show that SIRT4 levels decrease in the liver during fasting and that SIRT4 null mice display increased expression of hepatic peroxisome proliferator activated receptor (PPAR ) target genes associated with fatty acid catabolism. Accordingly, primary hepatocytes from SIRT4 knockout (KO) mice exhibit higher rates of fatty acid oxidation than wild-type hepatocytes, and SIRT4 overexpression decreases fatty acid oxidation rates. The enhanced fatty acid oxidation observed in SIRT4 KO hepatocytes requires functional SIRT1, demonstrating a clear cross talk between mitochondrial and nuclear sirtuins. Thus, SIRT4 is a new component of mitochondrial signaling in the liver and functions as an important regulator of lipid metabolism.
SIRT4 represses peroxisome proliferator-activated receptor α activity to suppress hepatic fat oxidation.
Sex, Specimen part
View SamplesNMNAT1 is a nuclear enzyme in the mammalian NAD+ salvage pathway. Expression microarray analysis was used to study the effect of NMNAT1 knockdown on gene expression in MCF-7 breast cancer cells.
Enzymes in the NAD+ salvage pathway regulate SIRT1 activity at target gene promoters.
No sample metadata fields
View SamplesSIRT1 is a nuclear NAD+-dependent protein deacetylase. Expression microarray analysis was used to study the effect of SIRT1 knockdown on gene expression in MCF-7 breast cancer cells.
Enzymes in the NAD+ salvage pathway regulate SIRT1 activity at target gene promoters.
No sample metadata fields
View SamplesNAMPT is an enzyme in the mammalian NAD+ salvage pathway. Expression microarray analysis was used to study the effect of NAMPT knockdown on gene expression in MCF-7 breast cancer cells.
Enzymes in the NAD+ salvage pathway regulate SIRT1 activity at target gene promoters.
No sample metadata fields
View Samples