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| Status |
Public on Feb 15, 2012 |
| Title |
Examination of functional interplay between NMNAT-1 (a nuclear NAD+ synthase) and PARP-1 (a nuclear poly(ADP-ribose) polymerase) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by genome tiling array
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| Summary |
NMNAT-1 and PARP-1, two key enzymes in the NAD+ metabolic pathway, localize to the nucleus where integration of their enzymatic activities has the potential to control a variety of nuclear processes. Using a variety of biochemical, molecular, cell-based, and genomic assays, we show that NMNAT-1 and PARP-1 physically and functionally interact at target gene promoters in MCF-7 cells. Specifically, we show that PARP-1 recruits NMNAT-1 to promoters, where it produces NAD+ to support PARP-1 catalytic activity, but also enhances the enzymatic activity of PARP-1 independent of NAD+ production. Furthermore, using two-photon excitation microscopy, we show that NMNAT-1 catalyzes the production of NAD+ in a nuclear pool that may be distinct from other cellular compartments. In expression microarray experiments, depletion of NMNAT-1 or PARP-1 alters the expression of about 200 protein-coding genes each, with about 10% overlap between the two gene sets. NMNAT-1 enzymatic activity is required for PARP-1-dependent PARylation at the promoters of commonly regulated target genes, as well as the expression of those target genes. Collectively, our studies link the enzymatic activities of NMNAT-1 and PARP-1 to the regulation of a set of common target genes through functional interactions at target gene promoters.
We examined the co-localization of NMNAT-1 and PARP-1 at RefSeq promoters in MCF-7 cells using ChIP-chip
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| Overall design |
Five samples:(1) two FLAG-NMNAT-1 IP'd with FLAG antibody from MCF-7 cells ectopically expressig FLAG-NMNAT-1 and (2) three native PARP-1 IP'd from parental MCF-7 cells with PARP-1 antibody
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| Contributor(s) |
Kraus WL, Zhang T |
| Citation(s) |
22334709 |
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| Submission date |
Jan 26, 2012 |
| Last update date |
Sep 20, 2012 |
| Contact name |
W. Lee Kraus |
| E-mail(s) |
lee.kraus@utsouthwestern.edu
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| Organization name |
UT Southwestern Medical Center
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| Street address |
5323 Harry Hines Blvd.
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| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390-8511 |
| Country |
USA |
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| Platforms (1) |
| GPL13752 |
Human_HG18_Deluxe_Promoter_HX1_HD2.1 tiling array |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA152743 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE35358_RAW.tar |
639.5 Mb |
(http)(custom) |
TAR (of PAIR, TXT) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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