scholarly journals Overexpression of Transcription Factor Sp1 Leads to Gene Expression Perturbations and Cell Cycle Inhibition

PLoS ONE ◽  
2009 ◽  
Vol 4 (9) ◽  
pp. e7035 ◽  
Author(s):  
Emmanuelle Deniaud ◽  
Joël Baguet ◽  
Roxane Chalard ◽  
Bariza Blanquier ◽  
Lilia Brinza ◽  
...  
Author(s):  
Arthur M Lesk ◽  
Arun S Konagurthu

Abstract Motivation The gene expression regulatory network in yeast controls the selective implementation of the information contained in the genome sequence. We seek to understand how, in different physiological states, the network reconfigures itself to produce a different proteome. Results This article analyses this reconfiguration, focussing on changes in the local structure of the network. In particular, we define, extract and compare the 1-neighbourhoods of each transcription factor, where a 1-neighbourhood of a node in a network is the minimal subgraph of the network containing all nodes connected to the central node by an edge. We report the similarities and differences in the topologies and connectivities of these neighbourhoods in five physiological states for which data are available: cell cycle, DNA damage, stress response, diauxic shift and sporulation. Based on our analysis, it seems apt to regard the components of the regulatory network as ‘software’, and the responses to changes in state, ‘reprogramming’.


2004 ◽  
Vol 24 (2) ◽  
pp. 865-874 ◽  
Author(s):  
Michelle A. Christensen ◽  
Weihui Zhou ◽  
Hong Qing ◽  
Anna Lehman ◽  
Sjaak Philipsen ◽  
...  

ABSTRACT Proteolytic processing of the β-amyloid precursor protein (APP) at the β site is essential to generate Aβ. BACE1, the major β-secretase involved in cleaving APP, has been identified as a type 1 membrane-associated aspartyl protease. We have cloned a 2.1-kb fragment upstream of the human BACE1 gene and identified key regions necessary for promoter activity. BACE1 gene expression is controlled by a TATA-less promoter. The region of bp −619 to +46 is the minimal promoter to control the transcription of the BACE1 gene. Several putative cis-acting elements, such as a GC box, HSF-1, a PU box, AP1, AP2, and lymphokine response element, are found in the 5′ flanking region of the BACE1 gene. Transcriptional activation and gel shift assays demonstrated that the BACE1 promoter contains a functional Sp1 response element, and overexpression of the transcription factor Sp1 potentiates BACE gene expression and APP processing to generate Aβ. Furthermore, Sp1 knockout reduced BACE1 expression. These results suggest that BACE1 gene expression is tightly regulated at the transcriptional level and that the transcription factor Sp1 plays an important role in regulation of BACE1 to process APP generating Aβ in Alzheimer's disease.


Diabetes ◽  
2014 ◽  
Vol 63 (12) ◽  
pp. 4165-4171 ◽  
Author(s):  
Q. Fang ◽  
W. Yang ◽  
H. Li ◽  
W. Hu ◽  
L. Chen ◽  
...  

1998 ◽  
Vol 18 (12) ◽  
pp. 7106-7118 ◽  
Author(s):  
Katherine A. Eliassen ◽  
Amy Baldwin ◽  
Eric M. Sikorski ◽  
Myra M. Hurt

ABSTRACT Expression of the highly conserved replication-dependent histone gene family increases dramatically as a cell enters the S phase of the eukaryotic cell cycle. Requirements for normal histone gene expression in vivo include an element, designated α, located within the protein-encoding sequence of nucleosomal histone genes. Mutation of 5 of 7 nucleotides of the mouse H3.2 α element to yield the sequence found in an H3.3 replication-independent variant abolishes the DNA-protein interaction in vitro and reduces expression fourfold in vivo. A yeast one-hybrid screen of a HeLa cell cDNA library identified the protein responsible for recognition of the histone H3.2 α sequence as the transcription factor Yin Yang 1 (YY1). YY1 is a ubiquitous and highly conserved transcription factor reported to be involved in both activation and repression of gene expression. Here we report that the in vitro histone α DNA-protein interaction depends on YY1 and that mutation of the nucleotides required for the in vitro histone α DNA-YY1 interaction alters the cell cycle phase-specific up-regulation of the mouse H3.2 gene in vivo. Because all mutations or deletions of the histone α sequence both abolish interactions in vitro and cause an in vivo decrease in histone gene expression, the recognition of the histone α element by YY1 is implicated in the correct temporal regulation of replication-dependent histone gene expression in vivo.


2004 ◽  
Vol 32 (6) ◽  
pp. 967-972 ◽  
Author(s):  
C.J. McInerny

A fundamental process in biology is the mechanism by which cells duplicate and divide to produce two identical daughter cells. The fission yeast, Schizosaccharomyces pombe, has proved to be an excellent model organism to study the role that gene expression plays in this process. The basic paradigm emerging is that a number of groups of genes are expressed in successive waves at different cell cycle times. Transcription of a particular group is controlled by a common DNA motif present in each gene's promoter, bound by a transcription factor complex. Each motif and transcription factor complex is specific to the time in the cell cycle when the group of genes is expressed. Examples of this are the MBF (MCB-binding factor)/MCB (MluI cell cycle box) system controlling gene expression at the start of S-phase, and PBF (PCB-binding factor)/PCB (Pombe cell cycle box) regulation of transcription at the end of mitosis. In some cases, these transcription control systems also operate during the alternative form of cell division, meiosis.


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