|
| 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.
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| |
|
| 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.
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| |
|
| 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 |
| E-mail(s) |
lee.kraus@utsouthwestern.edu
|
| 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)
|
| GSM324900 |
MCF-7 SIRT1 Replicate 1 |
| GSM324901 |
MCF-7 SIRT1 Replicate 2 |
| GSM324902 |
MCF-7 SIRT1 Replicate 3 |
| GSM339268 |
MCF-7 cells_luciferase matching NAMPT_replicate 1 |
| GSM339269 |
MCF-7 cells_luciferase matching NAMPT_replicate 2 |
| GSM339270 |
MCF-7 cells_luciferase matching NAMPT_replicate 3 |
| GSM339271 |
MCF-7 cells_NAMPT knockdown_replicate 1 |
| GSM339272 |
MCF-7 cells_NAMPT knockdown_replicate 2 |
| GSM339273 |
MCF-7 cells_NAMPT knockdown_replicate 3 |
| GSM339381 |
MCF-7 cells_luciferase knockdown_control_replicate 1 |
| GSM339382 |
MCF-7 cells_luciferase knockdown_control_replicate 3 |
| GSM339383 |
MCF-7 cells_luciferase knockdown_E2_replicate 1 |
| GSM339411 |
MCF-7 cells_luciferase knockdown_E2_replicate 3 |
| GSM339417 |
MCF-7 cells_NMNAT1 knockdown_control_replicate 1 |
| GSM339418 |
MCF-7 cells_NMNAT1 knockdown_control_replicate 3 |
| GSM339419 |
MCF-7 cells_NMNAT1 knockdown_E2_replicate 1 |
| GSM339420 |
MCF-7 cells_NMNAT1 knockdown_E2_replicate 3 |
| GSM339421 |
MCF-7 cells_luciferase knockdown_control_replicate 2 |
| GSM339422 |
MCF-7 cells_luciferase knockdown_E2_replicate 2 |
| GSM339423 |
MCF-7 cells_NMNAT1 knockdown_E2_replicate 2 |
| GSM339424 |
MCF-7 cells_NMNAT1 knockdown_control_replicate 2 |
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| 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 |
|
| Relations |
| BioProject |
PRJNA110679 |
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