Repression of the RHOH gene by JunD

2011 ◽  
Vol 437 (1) ◽  
pp. 75-88 ◽  
Author(s):  
Laure Delestré ◽  
Céline Berthon ◽  
Bruno Quesnel ◽  
Martin Figeac ◽  
Jean-Pierre Kerckaert ◽  
...  
Keyword(s):  
Cell Line ◽  
Gene Transcription ◽  
Promoter Region ◽  
Raji Cell ◽  
Minimal Promoter ◽  
Cell Leukaemia ◽  
Aberrant Expression ◽  
Leukaemia Cell Line ◽  
Quantitative Expression ◽  
Minimal Promoter Region

RhoH is a member of the Rho family of small GTP-binding proteins that lacks GTPase activity. Since RhoH is constantly bound by GTP, it is thought to be constitutively active and controlled predominantly by changes in quantitative expression. RhoH is produced specifically in haematopoietic cells and aberrant expression has been linked to various forms of leukaemia. Transcription of the RHOH gene is the first level at which the quantitative levels of the RhoH protein are regulated. Previous studies have demonstrated that RHOH gene transcription is initiated by three distinct promoter regions designated P1, P2 and P3 that define the 5′ end of exons 1, 2 and 4 respectively. In the present study we report that the P3 promoter is largely responsible for RHOH gene transcription in the B-lymphocytic cell line Raji. The P3 promoter contains a minimal promoter region and a repressor region extending from −236 to +67 and +68 to +245 respectively, relative to the 5′ end of exon 4. Chromatin immunoprecipitation demonstrated that two AP1 (activator protein 1) sites in the minimal promoter region bind JunD. When JUND is overexpressed, the endogenous RHOH gene is repressed; however, when JUND is inhibited, expression of endogenous RHOH is induced both in the Raji cell line and AML (acute myeloid leukaemia) cells. In the HCL (hairy cell leukaemia) cell line JOK-1, induction of RHOH increases expression of the α isoform of protein kinase C. This downstream target of RHOH is also induced in AML cells by JUND inhibition. Collectively, these data indicate that JunD is an inhibitor of RHOH gene expression.

Sp1 and Sp3 mediate NHE2 gene transcription in the intestinal epithelial cells

2007 ◽  
Vol 293 (1) ◽  
pp. G146-G153 ◽  
Author(s):  
Ping Hua ◽  
Hua Xu ◽  
Jennifer K. Uno ◽  
Maciej A. Lipko ◽  
Jiali Dong ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Epithelial Cells ◽  
Gene Transcription ◽  
Promoter Region ◽  
Promoter Activity ◽  
Intestinal Epithelial Cells ◽  
Gene Promoter ◽  
Minimal Promoter ◽  
Intestinal Epithelial ◽  
Minimal Promoter Region

Our previous studies have identified a minimal Sp1-driven promoter region (nt −36/+116) directing NHE2 expression in mouse renal epithelial cells. However, this minimal promoter region was not sufficient to support active transcription of NHE2 gene in the intestinal epithelial cells, suggesting the need for additional upstream regulatory elements. In the present study, we used nontransformed rat intestinal epithelial (RIE) cells as a model to identify the minimal promoter region and transcription factors necessary for the basal transcription of rat NHE2 gene in the intestinal epithelial cells. We identified a region within the rat NHE2 gene promoter located within nt −67/−43 upstream of transcription initiation site as indispensable for the promoter function in intestinal epithelial cells. Mutations at nt −56/−51 not only abolished the DNA-protein interaction in this region, but also completely abolished NHE2 gene promoter activity in RIE cells. Supershift assays revealed that Sp1 and Sp3 interact with this promoter region, but, contrary to the minimal promoter indispensable for renal expression of NHE2, both transcription factors expressed individually in Drosophila SL2 cells activated rat NHE2 gene promoter. Moreover, Sp1 was a weaker transactivator and when coexpressed in SL2 cells it reduced Sp3-mediated NHE2 basal promoter activity. Furthermore, DNase I footprinting confirmed that nt −58/−51 is protected by nuclear protein from RIE cells. We conclude that the mechanism of basal control of rat NHE2 gene promoter activity is different in the renal and intestinal epithelium, with Sp3 being the major transcriptional activator of NHE2 gene transcription in the intestinal epithelial cells.

RUNX1 and GATA2 Regulate the Expression of the SET Oncogene in Acute Myeloid Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 879-879
Author(s):  
Raffaella Pippa ◽  
Ana Dominguez ◽  
Nerea Marcotegui ◽  
Raquel Malumbres ◽  
Elizabeth Guruceaga ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Promoter Region ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Minimal Promoter ◽  
Research Network ◽  
Luciferase Reporter ◽  
Prognostic Impact ◽  
Minimal Promoter Region ◽  
Acute Myeloid

Abstract INTRODUCTION. The protein SET (I2PP2A), a potent protein phosphatase 2A (PP2A) inhibitor, has been implicated in many cell processes such as DNA replication, chromatin remodeling and gene transcription, differentiation, migration, and cell-cycle regulation. In fact, SET has been described as an oncogene that regulates important signaling pathways. Our group reported that PP2A inhibition is a common event in AML, and that SET is overexpressed in 28% of acute myeloid leukemia (AML) cases, where it is associated with short overall survival. Moreover, the anti-leukemic effects of the FTY720 and OP449 PP2A-activating drugs in AML cells depend on interaction/sequestration of SET. However, despite the importance of SET overexpression and its prognostic impact in both hematological and solid tumors, there are few data about the mechanisms involved in its regulation. AIM. To characterize the functional promoter region of the SET gene, and to identify transcription factors (TFs) involved in its regulation. RESULTS. Luciferase reporter assays with five truncatedconstructs allowed us to determine a 163bp-region as the minimal promoter region of SET that contains consensus sites for several TFs. Chromatin immunoprecipitation (ChIP) assays confirmed the binding of RUNX1, GATA2, MYC, and SP1. RUNX1 and GATA2 are two essential TFs in hematopoiesis, and localized on the SET promoter when the acetylation state of both histone H3 and H4 and the tri-methylation on H3K4 is high, confirming that they both could act as positive regulators of SET transcription. In silico analysis in large series of adult patient samples with de novo AML recently published by The Cancer Genome Atlas Research Network showed a significant positive correlation between SET and RUNX1 and GATA2 at mRNA level. Furthermore, knockdown of RUNX1 and/or GATA2 triggered SET downregulation, whereas only a simultaneous overexpression of these two TFs caused a significant up-regulation of SET. Interestingly, RUNX1 interacts with GATA2 in both HL-60 and HEL cell lines. Moreover, we found that SP1 is also part of this transcription complex. Altogether, these results show that RUNX1 and GATA2, together with SP1, regulate the transcription of the SET gene. CONCLUSIONS We have defined the minimal promoter region of the SET gene, and have demonstrated that RUNX1 and GATA2 regulate its expression in AML. Moreover, our functional studies demonstrate that RUNX1 and GATA2 form a complex with SP1 that activates the transcription of SET in AML cells. This study opens new directions to further understand the mechanisms of SET overexpressing leukemias. Disclosures No relevant conflicts of interest to declare.

A novel canine B-cell leukaemia cell line. Establishment, characterisation and sensitivity to chemotherapeutics

2016 ◽  
Vol 15 (4) ◽  
pp. 1218-1231 ◽  
Author(s):  
A. Pawlak ◽  
E. Ziolo ◽  
J. Kutkowska ◽  
A. Blazejczyk ◽  
J. Wietrzyk ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Line ◽  
Cell Leukaemia ◽  
Leukaemia Cell ◽  
Leukaemia Cell Line ◽  
Cell Line Establishment

scholarly journals cis- and trans-Acting Elements Involved in Regulation of aniA, the Gene Encoding the Major Anaerobically Induced Outer Membrane Protein inNeisseria gonorrhoeae

1999 ◽  
Vol 181 (2) ◽  
pp. 541-551 ◽  
Author(s):  
Tracey C. Householder ◽  
Wesley A. Belli ◽  
Sarah Lissenden ◽  
Jeffrey A. Cole ◽  
Virginia L. Clark
Keyword(s):  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Promoter Region ◽  
Site Directed Mutagenesis ◽  
Minimal Promoter ◽  
Upstream Region ◽  
Gene Encoding ◽  
Sigma 70 ◽  
Minimal Promoter Region

ABSTRACT AniA (formerly Pan1) is the major anaerobically induced outer membrane protein in Neisseria gonorrhoeae. AniA has been shown to be a major antigen in patients with gonococcal disease, and we have been studying its regulation in order to understand the gonococcal response to anaerobiosis and its potential role in virulence. This study presents a genetic analysis of aniA regulation. Through deletion analysis of the upstream region, we have determined the minimal promoter region necessary for aniA expression. This 130-bp region contains a sigma 70-type promoter and an FNR (fumarate and nitrate reductase regulator protein) binding site, both of which are absolutely required for anaerobic expression. Also located in the minimal promoter region are three T-rich direct repeats and several potential NarP binding sites. This 80-bp region is required for induction by nitrite. By site-directed mutagenesis of promoter sequences, we have determined that the transcription ofaniA is initiated only from the sigma 70-type promoter. The gearbox promoter, previously believed to be the major promoter, does not appear to be active during anaerobiosis. The gonococcal FNR and NarP homologs are involved in the regulation of aniA, and we demonstrate that placing aniA under the control of thetac promoter compensates for the inability of a gonococcalfnr mutant to grow anaerobically.

scholarly journals Multiple Functional Sp1 Domains in the Minimal Promoter Region of the Neuronal Nicotinic Receptor α5 Subunit Gene

1999 ◽  
Vol 274 (8) ◽  
pp. 4693-4701 ◽  
Author(s):  
Antonio Campos-Caro ◽  
Carmen Carrasco-Serrano ◽  
Luis M. Valor ◽  
Salvador Viniegra ◽  
Juan J. Ballesta ◽  
...  
Keyword(s):  
Nicotinic Receptor ◽  
Promoter Region ◽  
Minimal Promoter ◽  
Subunit Gene ◽  
Neuronal Nicotinic Receptor ◽  
Minimal Promoter Region

Regulatory elements in the minimal promoter region of the mouse Xist gene

Gene ◽  
1997 ◽  
Vol 203 (2) ◽  
pp. 159-168 ◽  
Author(s):  
S.A Sheardown ◽  
A.E.T Newall ◽  
D.P Norris ◽  
S Rastan ◽  
N Brockdorff
Keyword(s):  
Promoter Region ◽  
Regulatory Elements ◽  
Xist Gene ◽  
Minimal Promoter ◽  
Minimal Promoter Region

scholarly journals Identification of regulatory elements within the minimal promoter region of the human endogenous ERV9 proviruses: accurate transcription initiation is controlled by an Inr-like element

1992 ◽  
Vol 20 (16) ◽  
pp. 4129-4136 ◽  
Author(s):  
Girolama La Mantia ◽  
Barbara Majello ◽  
Antonio Di Cristofano ◽  
Maria Strazzullo ◽  
Gabriella Minchiotti ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
Promoter Region ◽  
Regulatory Elements ◽  
Minimal Promoter ◽  
Minimal Promoter Region
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