JC Virus Multiplication in Human Hematopoietic Progenitor Cells Requires the NF-1 Class D Transcription Factor

Monaco, Maria Chiara; Sabath, Bruce F.; Durham, Linda C.; Major, Eugene O.

doi:10.1128/jvi.75.20.9687-9695.2001

Cited by 71 publications

(80 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The extensive defects in the brain development in NFia and NFib knock-out animals suggest that some NFI isoforms are critical for proper development of the central nervous system. In addition, overexpression of the NFI-X protein (also known as NFI class D) supports replication of the human JC polyomavirus, which specifically targets glial cells and causes demyelinating disease (38). Our results, proposing a central role for NFI-X in astrocyte-specific expression of the ACT and GFAP genes, extend previous findings indicating that NFI isoforms are critical for brain development.…”

Section: Discussionsupporting

confidence: 81%

Nuclear Factor-1-X Regulates Astrocyte-specific Expression of the α1-Antichymotrypsin and Glial Fibrillary Acidic Protein Genes

Gopalan

Wilczynska

Konik

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

Discrete tissue-specific changes in chromatin structure of the distal serpin subcluster on human chromosome 14q32.1 allow a single gene encoding ␣ 1 -antichymotrypsin (ACT) to be expressed in astrocytes and glioma cells. This astrocyte-specific regulation involves activatory protein-1 (AP-1) because overexpression of dominantnegative c-jun(TAM67) abolishes ACT expression in glioma cells. Here we identify a new regulatory element, located within the ؊13-kb enhancer of the ACT gene, that binds nuclear factor-1 (NFI) and is indispensable for the full basal transcriptional activity of the ACT gene. Furthermore, down-regulation of NFI expression by siRNA abolishes basal ACT expression in glioma cells. However, NFI does not mediate astrocyte-specific expression by itself, but likely cooperates with AP-1. A detailed analysis of the 14-kb long 5-flanking region of the ACT gene indicated the presence of adjacent NFI and AP-1 elements that colocalized with DNase I-hypersensitive sites found in astrocytes and glioma cells. Interestingly, knock-down of NFI expression also specifically abrogates the expression of glial acidic fibrillary protein (GFAP), which is an astrocyte-specific marker protein. Mutations introduced into putative NFI and AP-1 elements within the 5-flanking region of the GFAP gene also diminished basal expression of the reporter. In addition, we found, using isoform-specific siRNAs, that NFI-X regulates the astrocytespecific expression of ACT and GFAP. We propose that NFI-X cooperates with AP-1 by an unknown mechanism in astrocytes, which results in the expression of a subset of astrocyte-specific genes.2 is expressed at low levels by astrocytes in the brain under normal physiological conditions. However, elevated ACT levels have been observed in several neuropathological disorders of the central nervous system, including Alzheimer disease (1, 2). This drastic change in ACT expression is caused by proinflammatory cytokines, including IL-1, IL-6, oncostatin M (OSM), and tumor necrosis factor (TNF)␣, which are released at the site of tissue damage (3, 4). ACT secreted by reactive astrocytes subsequently associates with the ␤-amyloid peptide, which is the major component of pathological deposits found in the brains of Alzheimer disease patients (1).ACT belongs to the serine protease inhibitor (serpin) family of proteins and is also expressed in the liver and secreted into the plasma (5). The gene encoding ACT is clustered with 10 additional serpin genes on human chromosome 14q32.1 and resides within the distal serpin subcluster that also contains genes encoding kallistatin, protein C inhibitor, and the kallistatin-like protein (6, 7). The expression profile of the distal serpin subcluster is dramatically different between astrocytes and hepatocytes. All four genes are expressed in hepatocytes, whereas only the ACT gene is expressed in astrocytes (8). Investigations of the regulatory mechanisms controlling the selective expression of ACT in astrocytes and glioma cells demonstrated that the ACT gene is localize...

show abstract

Section: Discussionsupporting

confidence: 81%

Nuclear Factor-1-X Regulates Astrocyte-specific Expression of the α1-Antichymotrypsin and Glial Fibrillary Acidic Protein Genes

Gopalan

Wilczynska

Konik

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Formed complexes were washed extensively with lysis buffer and resolved by SDS-10% PAGE followed by Western blot analysis with anti-Jun antibody (KM-1; Santa Cruz). Alternatively, 4 l of 35 Slabeled in vitro-translated full-length c-Jun was incubated with GST alone or full-length GST-c-Jun fusion protein immobilized on glutathione-Sepharose beads. All reactions were performed in 400 l of total reaction volume in lysis buffer overnight at 4°C with continuous rocking.…”

Section: Methodsmentioning

confidence: 99%

“…The viral genome is composed of regulatory and coding regions. The regulatory region contains DNA target sequences for both viral and cellular transcription factors, including NF-B (39,45), Tst-1 (41,60), NF-1 (1,2,35), Sp-1 (20), GBP-i (38), YB-1 (24,44,46,48), and Pur␣ (11,46). The viral coding regions encode early regulatory proteins (small t, large T, and isoforms of early proteins, TЈ) and late structural capsid proteins (VP-1, VP-2, and VP-3).…”

mentioning

confidence: 99%

Members of the AP-1 Family, c-Jun and c-Fos, Functionally Interact with JC Virus Early Regulatory Protein Large T Antigen

Kim

Woolridge

Biffi

et al. 2003

J Virol

View full text Add to dashboard Cite

“…The host cell type specificity can be controlled through transcriptional blocks to infection as well as virus-receptor interactions (3,7,19). Previous work evaluating the role of minor coat proteins in the related polyomavirus simian virus 40 (SV40) found that Vp2 was dispensable but that Vp3 was necessary for infection.…”

mentioning

confidence: 99%

JC Virus Minor Capsid Proteins Vp2 and Vp3 Are Essential for Virus Propagation

Gasparovic

Gee

Atwood

2006

J Virol

View full text Add to dashboard Cite

Virus-encoded capsid proteins play a major role in the life cycles of all viruses. The JC virus capsid is composed of 72 pentamers of the major capsid protein Vp1, with one of the minor coat proteins Vp2 or Vp3 in the center of each pentamer. Vp3 is identical to two-thirds of Vp2, and these proteins share a DNA binding domain, a nuclear localization signal, and a Vp1-interacting domain. We demonstrate here that both the minor proteins and the myristylation site on Vp2 are essential for the viral life cycle, including the proper packaging of its genome.

show abstract

JC Virus Multiplication in Human Hematopoietic Progenitor Cells Requires the NF-1 Class D Transcription Factor

Cited by 71 publications

References 49 publications

Nuclear Factor-1-X Regulates Astrocyte-specific Expression of the α1-Antichymotrypsin and Glial Fibrillary Acidic Protein Genes

Nuclear Factor-1-X Regulates Astrocyte-specific Expression of the α1-Antichymotrypsin and Glial Fibrillary Acidic Protein Genes

Members of the AP-1 Family, c-Jun and c-Fos, Functionally Interact with JC Virus Early Regulatory Protein Large T Antigen

JC Virus Minor Capsid Proteins Vp2 and Vp3 Are Essential for Virus Propagation

Contact Info

Product

Resources

About