Characterization of a novel quiescence responsive element downregulated by v-Src in the promoter of the neuroretina specific QR1 gene

Abstract

The neuroretina is a functional unit of the central nervous system which arises through successive steps of division, growth arrest and di erentiation of neuroectodermal precursors. Postmitotic quail neuroretina (QNR) cells are conditionally induced to divide upon infection with temperature sensitive mutants of Rous sarcoma virus (RSV), since QNR cell division can be arrested by either inactivating p60v-Src at the nonpermissive temperature (418C) or by serum deprivation at 378C. We are studying the transcriptional control of QR1, a neuroretina speci®c gene, whose expression is downregulated in proliferating cells at 378C and is fully restored when these cells are made quiescent. We previously showed that this quiescence speci®c upregulation implicates a promoter region named A box, which binds Maf transcription factors. We report the identi®-cation of the C box, a second promoter sequence that activates QR1 transcription in non dividing cells. This sequence is able to form two DNA-protein complexes, one of which (C4) is predominantly detected in growth arrested NR cells. We identi®ed the DNA binding site for C4 and described mutations that abolish both C4 binding and promoter activity in quiescent cells. Moreover, we show that a multimerized C box is able to stimulate a heterologous promoter in non dividing cells and constitutes, therefore, a novel quiescence responsive enhancer. Finally, we report that QR1 transcriptional response to cell quiescence requires cooperation between the C box and A box. Oncogene (2000) 19, 4736 ± 4745.

SSeCKS/Gravin/AKAP12 attenuates expression of proliferative and angiogenic genes during suppression of v-Src-induced oncogenesis

“…The increased levels of the transcription factors Maff, Runx1 and Etv4, and the decreased levels of Centd3, Id4, Spon2, and Cbr2 by v-Src seem to directly relate to cancer progression. Specifically, Maff is overexpressed in some forms of cancer [ 38 ] and Maf proteins play direct roles in controlling v-Src-regulated gene expression [ 39 ]. Runx1 induces cell cycle progression [ 40 ] and increased Runx1 levels are found in chronic myelogenous leukemias [ 41 ].…”

Rhodopsin, Violet and Blue Opsin Expressions in the Chick Are Highly Dependent on Tissue and Serum Conditions

“…Thus by providing decisive environmental cues, the applied concentration of serum was most critical. Specifi c serum response elements within key transcription factors, such as Nrl or the various Maf factors, may well pilot selective photoreceptor differentiation [Provot et al, 2000;Lerner et al, 2001]. A decisive infl uence of a 3-dimensional tissue environment was demonstrated by our reaggregation experiments (rosetted retinal spheres), representing models of 3-dimensional tissue reconstruction [Layer et al, , 2002.…”

v-Src-mediated Down-regulation of SSeCKS Metastasis Suppressor Gene Promoter by the Recruitment of HDAC1 into a USF1-Sp1-Sp3 Complex

“…With the exception of studies on the QR1 gene (50,54), little is known regarding the mechanism by which v-Src down-regulates gene transcription. In this study, we used the ssecks gene as a prototype in order to explore the mechanisms involved in v-Src-mediated gene repression.…”