Poly(ADP-ribose) polymerase-1 (PARP-1) transcriptionally regulates angiotensin AT2 receptor (AT2R) and AT2R binding protein (ATBP) genes

Abstract

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 2 ABSTRACTThe renin-angiotensin system (RAS) plays a crucial role in cardiovascular and neuronal (patho-)physiology. The angiotensin AT2 receptor (AT2R) seems to counteract the proinflammatory, prohypertrophic and profibrotic actions of the AT1receptor. Recently, we identified a novel protein, termed "AT2R binding protein" (ATBP/ ATIP) which seems essential for AT2R mediated growth inhibition.Poly(ADP-ribose) polymerase-1 (PARP-1) can act as a nuclear integrator of angiotensin II-mediated cell signalling, and has been implicated in the pathogenesis of cardiovascular and neuronal disease.In this study, promoters of human AT2R and ATIP1 were cloned and two transcriptional start sites in the ATIP1 promoter were identified whereas only one was detected in the AT2R promoter. Promoter assays indicated that the exon 1-intron 1 region of AT2R is necessary and sufficient for AT2R promoter activity.Inverse cloning experiments indicated that this regulatory region is a promoter but not an enhancer element implicating (a) further start site(s) in this region.

Functional Aspects of PARP1 in DNA Repair and Transcription

“…Transcriptional regulation by PARP1 involves both ADP-ribosylation-dependent and independent mechanisms (Figure 3). Furthermore, PARP1 exerts its effects on transcription both in a DNA sequence-dependent and independent manner, through motif recognition at specific gene promoters [24,25,26,27,30,115,116,117,118,119,120,121,122,123] and chromatin remodeling [20,22], respectively. …”

Microtubule associated tumor suppressor 1 deficient mice develop spontaneous heart hypertrophy and SLE-like lymphoproliferative disease

“…A recently published study reveals that Poly(ADP-ribose) polymerase-1 (PARP-1) can activate the transcription of the MTUS1 gene and represses the AT2R transcription (15). PARP-1 is known to be involved in diseases like hypertension and inflammation, although PARP-1 deficient mice do not develop cardiac hypertrophy (16).…”

p53 regulates the expression of human angiotensin II AT2 receptor interacting protein (ATIP1) gene

“…1B). The ATIP1 promoter activity has also been independently confirmed in a breast cancer cell line (MCF7) and a human endothelial cell (EA.hy926) (14). These results suggest that the promoter for the ATIP1 gene is ubiquitous (independent of cell type).…”

“…We have already confirmed the predicted transcript start site of the ATIP1 gene, which is orthologously conserved (7). An additional transcription start site has been detected in cardiac cells (left ventricle), which is located 10 bp upstream of the conserved transcription start site (14). However, this alternative transcription start site was not detected in our cell line using 5′ RACE.…”