Article
CIITA mediates interferon-gamma repression of collagen transcription through phosphorylation-dependent interactions with co-repressor molecules.
Department of Biochemistry, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
Journal of Biological Chemistry (impact factor:
4.77).
02/2008;
283(3):1243-56.
DOI:10.1074/jbc.M707180200
pp.1243-56
Source: PubMed
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Citations (0)
- Cited In (3)
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Article: Sin3: master scaffold and transcriptional corepressor.
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ABSTRACT: Sin3 was isolated over two decades ago as a negative regulator of transcription in budding yeast. Subsequent research has established the protein as a master transcriptional scaffold and corepressor capable of transcriptional silencing via associated histone deacetylases (HDACs). The core Sin3-HDAC complex interacts with a wide variety of repressors and corepressors, providing flexibility and expanded specificity in modulating chromatin structure and transcription. As a result, the Sin3/HDAC complex is involved in an array of biological and cellular processes, including cell cycle progression, genomic stability, embryonic development, and homeostasis. Abnormal recruitment of this complex or alteration of its enzymatic activity has been implicated in neoplastic transformation.Biochimica et Biophysica Acta 07/2009; 1789(6-8):443-50. · 4.66 Impact Factor -
Article: Tumor suppressor protein p53 recruits human Sin3B/HDAC1 complex for down-regulation of its target promoters in response to genotoxic stress.
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ABSTRACT: Master regulator protein p53, popularly known as the "guardian of genome" is the hub for regulation of diverse cellular pathways. Depending on the cell type and severity of DNA damage, p53 protein mediates cell cycle arrest or apoptosis, besides activating DNA repair, which is apparently achieved by regulation of its target genes, as well as direct interaction with other proteins. p53 is known to repress target genes via multiple mechanisms one of which is via recruitment of chromatin remodelling Sin3/HDAC1/2 complex. Sin3 proteins (Sin3A and Sin3B) regulate gene expression at the chromatin-level by serving as an anchor onto which the core Sin3/HDAC complex is assembled. The Sin3/HDAC co-repressor complex can be recruited by a large number of DNA-binding transcription factors. Sin3A has been closely linked to p53 while Sin3B is considered to be a close associate of E2Fs. The theme of this study was to establish the role of Sin3B in p53-mediated gene repression. We demonstrate a direct protein-protein interaction between human p53 and Sin3B (hSin3B). Amino acids 1-399 of hSin3B protein are involved in its interaction with N-terminal region (amino acids 1-108) of p53. Genotoxic stress induced by Adriamycin treatment increases the levels of hSin3B that is recruited to the promoters of p53-target genes (HSPA8, MAD1 and CRYZ). More importantly recruitment of hSin3B and repression of the three p53-target promoters upon Adriamycin treatment were observed only in p53(+/+) cell lines. Additionally an increased tri-methylation of the H3K9 residue at the promoters of HSPA8 and CRYZ was also observed following Adriamycin treatment. The present study highlights for the first time the essential role of Sin3B as an important associate of p53 in mediating the cellular responses to stress and in the transcriptional repression of genes encoding for heat shock proteins or proteins involved in regulation of cell cycle and apoptosis.PLoS ONE 01/2011; 6(10):e26156. · 4.09 Impact Factor -
Article: Interferon gamma (IFN-γ) disrupts energy expenditure and metabolic homeostasis by suppressing SIRT1 transcription.
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ABSTRACT: Chronic inflammation impairs metabolic homeostasis and is intimately correlated with the pathogenesis of type 2 diabetes. The pro-inflammatory cytokine IFN-γ is an integral part of the metabolic inflammation circuit and contributes significantly to metabolic dysfunction. The underlying mechanism, however, remains largely unknown. In the present study, we report that IFN-γ disrupts the expression of genes key to cellular metabolism and energy expenditure by repressing the expression and activity of SIRT1 at the transcription level. Further analysis reveals that IFN-γ requires class II transactivator (CIITA) to repress SIRT1 transcription. CIITA, once induced by IFN-γ, is recruited to the SIRT1 promoter by hypermethylated in cancer 1 (HIC1) and promotes down-regulation of SIRT1 transcription via active deacetylation of core histones surrounding the SIRT1 proximal promoter. Silencing CIITA or HIC1 restores SIRT1 activity and expression of metabolic genes in skeletal muscle cells challenged with IFN-γ. Therefore, our data delineate an IFN-γ/HIC1/CIITA axis that contributes to metabolic dysfunction by suppressing SIRT1 transcription in skeletal muscle cells and as such shed new light on the development of novel therapeutic strategies against type 2 diabetes.Nucleic Acids Research 11/2011; 40(4):1609-20. · 8.03 Impact Factor
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Keywords
CIITA represses collagen transcription
CIITA responsible
co-repressor molecules
collagen repression
collagen start site
collagen synthesis
collagen transcription
collagen type
decreases repression
glycogen synthase kinase 3
GSK3 site
histone deacetylase
IFN-gamma)-induced repression
IFN-gamma-mediated recruitment
major histocompatibility class II trans-activator
mediating IFN-gamma-induced inhibition
phosphorylation-dependent interaction
proline/serine/threonine domain
Sin3B
vitro phosphorylation
