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Series GSE13577 Query DataSets for GSE13577
Status Public on May 28, 2009
Title SIRT1-Dependent Gene Regulation Through Promoter-Directed Recruitment of a Nuclear NAD+ Synthase
Organism Homo sapiens
Experiment type Expression profiling by array
Summary In 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.

This SuperSeries is composed of the SubSeries listed below.
Overall design Refer to individual Series.
Each of the 3 Series has its own matching luciferase knockdown controls and the three data sets were generated independently of each other.
Contributor(s) Zhang T, Frizzell KM, Gamble MJ, Kraus WL
Citation(s) 19478080
Submission date Nov 12, 2008
Last update date Mar 25, 2019
Contact name W. Lee Kraus
Organization name UT Southwestern Medical Center
Street address 5323 Harry Hines Blvd.
City Dallas
State/province TX
ZIP/Postal code 75390-8511
Country USA
Platforms (2)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
Samples (24)
GSM324888 MCF-7 Luciferase Replicate 1
GSM324889 MCF-7 Luciferase Replicate 2
GSM324890 MCF-7 Luciferase Replicate 3
This SuperSeries is composed of the following SubSeries:
GSE13449 Expression analysis upon NAMPT knockdown in MCF-7 cells
GSE13458 Expression analysis upon NMNAT1 knockdown in MCF-7 cells
GSE13459 Expression analysis upon SIRT1 knockdown in MCF-7 cells
BioProject PRJNA110679

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE13577_RAW.tar 59.7 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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