scholarly journals Deacetylase Activity Is Required for Recruitment of the Basal Transcription Machinery and Transactivation by STAT5

2003 ◽  
Vol 23 (12) ◽  
pp. 4162-4173 ◽  
Author(s):  
Anne Rascle ◽  
James A. Johnston ◽  
Bruno Amati
Keyword(s):  
Chromatin Remodeling ◽  
Chromatin Immunoprecipitation ◽  
Transcription Initiation ◽  
Cellular Response ◽  
Target Genes ◽  
Trichostatin A ◽  
Basal Transcription ◽  
Basal Transcription Machinery ◽  
Transcription Machinery ◽  
Microarray Analyses

ABSTRACT The signal transducer and activator of transcription STAT5 plays a major role in the cellular response to cytokines, but the mechanism by which it activates transcription remains poorly understood. We show here that deacetylase inhibitors (trichostatin A, suberoylanilide hydroxamic acid, and sodium butyrate) prevent induction of endogenous STAT5 target genes, implying that a deacetylase activity is required for that process. Microarray analyses revealed that this requirement is common to all STAT5 target genes. Using chromatin immunoprecipitation, we show that, following STAT5 DNA binding, deacetylase inhibitors block transcription initiation by preventing recruitment of the basal transcription machinery. This inhibition is not due to effects on histone H3 and H4 acetylation or chromatin remodeling within the promoter region. This novel mechanism of transactivation by STAT5 provides a rationale for the use of deacetylase inhibitors for therapeutic intervention in STAT5-associated cancers.

scholarly journals The basal transcription machinery as a target for cancer therapy

2014 ◽  
Vol 14 (1) ◽  
pp. 18 ◽  
Author(s):  
Claudia Villicaña ◽  
Grisel Cruz ◽  
Mario Zurita
Keyword(s):  
Cancer Therapy ◽  
Basal Transcription ◽  
Basal Transcription Machinery ◽  
Transcription Machinery

scholarly journals The chromatin remodeler ISWI regulates the cellular response to hypoxia: role of FIH

2011 ◽  
Vol 22 (21) ◽  
pp. 4171-4181 ◽  
Author(s):  
Andrew Melvin ◽  
Sharon Mudie ◽  
Sonia Rocha
Keyword(s):  
Rna Polymerase Ii ◽  
Chromatin Remodeling ◽  
Cellular Response ◽  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylases ◽  
Additional Information ◽  
Protein Levels ◽  
Survival Factor

The hypoxia-inducible factor (HIF) is a master regulator of the cellular response to hypoxia. Its levels and activity are controlled by dioxygenases called prolyl-hydroxylases and factor inhibiting HIF (FIH). To activate genes, HIF has to access sequences in DNA that are integrated in chromatin. It is known that the chromatin-remodeling complex switch/sucrose nonfermentable (SWI/SNF) is essential for HIF activity. However, no additional information exists about the role of other chromatin-remodeling enzymes in hypoxia. Here we describe the role of imitation switch (ISWI) in the cellular response to hypoxia. We find that unlike SWI/SNF, ISWI depletion enhances HIF activity without altering its levels. Furthermore, ISWI knockdown only alters a subset of HIF target genes. Mechanistically, we find that ISWI is required for full expression of FIH mRNA and protein levels by changing RNA polymerase II loading to the FIH promoter. Of interest, exogenous FIH can rescue the ISWI-mediated upregulation of CA9 but not BNIP3, suggesting that FIH-independent mechanisms are also involved. Of importance, ISWI depletion alters the cellular response to hypoxia by reducing autophagy and increasing apoptosis. These results demonstrate a novel role for ISWI as a survival factor during the cellular response to hypoxia.

scholarly journals Cdc28 kinase activity regulates the basal transcription machinery at a subset of genes

2012 ◽  
Vol 109 (26) ◽  
pp. 10450-10455 ◽  
Author(s):  
P. Chymkowitch ◽  
V. Eldholm ◽  
S. Lorenz ◽  
C. Zimmermann ◽  
J. M. Lindvall ◽  
...  
Keyword(s):  
Kinase Activity ◽  
Basal Transcription ◽  
Basal Transcription Machinery ◽  
Transcription Machinery ◽  
Cdc28 Kinase

Purified cofactors and histone H1 mediate transcriptional regulation by CTF/NF-I

1992 ◽  
Vol 12 (11) ◽  
pp. 5228-5237
Author(s):  
Y Dusserre ◽  
N Mermod
Keyword(s):  
Rna Polymerase Ii ◽  
Regulatory Protein ◽  
Histone H1 ◽  
Regulation Of Transcription ◽  
Basal Transcription ◽  
Activator Proteins ◽  
Basal Transcription Machinery ◽  
Transcription Machinery ◽  
Transcriptional Cofactors

The initiation of RNA polymerase II transcription is controlled by DNA sequence-specific activator proteins, in combination with cofactor polypeptides whose function is poorly understood. Transcriptional cofactors of the CTF-1 activator were purified on the basis of their affinity for the regulatory protein. These purified cofactors were found to be required for CTF-1-regulated transcription, and they counteracted squelching by an excess of activator in in vitro reconstitution experiments. Interestingly, the cofactors possessed an inhibitory activity for basal transcription, which was relieved by the further addition of the activator. Histone H1 also contributes to the regulation of transcription by CTF-1, whereby the activator prevents repression of the basal transcription machinery by the histone. However, histone H1 could not replace the cofactors for CTF-1-regulated transcription, indicating that they possess distinct transcriptional properties. Furthermore, the purified cofactors were found to be required, together with the activator, in order to antagonize the histone-mediated repression of transcription. These results suggest that CTF-1 and its cofactors function by regulating the assembly of the basal transcription machinery onto the promoter when the latter is in competition with DNA-binding inhibitory proteins such as histone H1.

scholarly journals The Chromatin-Remodeling BAF Complex Mediates Cellular Antiviral Activities by Promoter Priming

2004 ◽  
Vol 24 (10) ◽  
pp. 4476-4486 ◽  
Author(s):  
Kairong Cui ◽  
Prafullakumar Tailor ◽  
Hong Liu ◽  
Xin Chen ◽  
Keiko Ozato ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Transcriptional Activation ◽  
Cellular Response ◽  
Target Genes ◽  
Baf Complex ◽  
Inducible Promoters ◽  
Rapid Induction ◽  
Antiviral Activities ◽  
Inducible Genes ◽  
Target Promoters

ABSTRACT The elicitation of cellular antiviral activities is dependent on the rapid transcriptional activation of interferon (IFN) target genes. It is not clear how the interferon target promoters, which are organized into chromatin structures in cells, rapidly respond to interferon or viral stimulation. In this report, we show that alpha IFN (IFN-α) treatment of HeLa cells induced hundreds of genes. The induction of the majority of these genes was inhibited when one critical subunit of the chromatin-remodeling SWI/SNF-like BAF complexes, BAF47, was knocked down via RNA interference. Inhibition of BAF47 blocked the cellular response to viral infection and impaired cellular antiviral activity by inhibiting many IFN- and virus-inducible genes. We show that the BAF complex was required to mediate both the basal-level expression and the rapid induction of the antiviral genes. Further analyses indicated that the BAF complex primed some IFN target promoters by utilizing ATP-derived energy to maintain the chromatin in a constitutively open conformation, allowing faster and more potent induction after IFN-α treatment. We propose that constitutive binding of the BAF complex is an important mechanism for the IFN-inducible promoters to respond rapidly to IFN and virus stimulation.

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