Dynamic Recruitment of NF-Y and Histone Acetyltransferases on Cell-cycle Promoters

Caretti, Giuseppina; Salsi, Valentina; Vecchi, Chiara; Imbriano, Carol; Mantovani, Roberto

doi:10.1074/jbc.m304606200

Cited by 144 publications

(164 citation statements)

References 49 publications

Supporting

Mentioning

148

Contrasting

Unclassified

Order By: Relevance

“…4A). NF-Y is a transcription factor that binds with high affinity and fidelity to CCAAT-containing consensus sequences and has also been described to be involved in cell cycle (22) and stem cell self-renewal (23).…”

Section: Resultsmentioning

confidence: 99%

Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer

Chia

Leung

Krushel

et al. 2008

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: The Epstein Barr virus (EBV) is intimately associated with nasopharyngeal cancer (NPC) in a latent state expressing a limited number of genes.The process of switching from latency to replication is not well understood, particularly in response to DNA stress; hence, the focus of this study is on an EBV-positive NPC model. Experimental Design: C666-1 cells were exposed to radiation (2-15 Gy) or cisplatin (0.1-50 Ag/mL) assayed subsequently for relative EBV copy number (BamHI) and lytic gene expression (BRLF1 and BZLF1) using quantitative real-time PCR. Chromatin immunoprecipitation was conducted to assess the interaction of the transcription factor nuclear factor-Y (NF-Y) with promoter sequences. Results: Radiation-induced and cisplatin-induced BamHI expression, along with increased levels of BRLF1 and BZLF1 in a dose-dependent and time-dependent manner, associated with the immediate nuclear transactivation of the transcription factor NF-Y and its own increased transcription of NF-Y subunits 8 h posttreatment. In silico analysis revealed three putative NF-Y consensus-binding sequences in the promoter region of BRLF1, which all interacted with NF-Y in response to radiation and cisplatin, confirmed using chromatin immunoprecipitation. Introduction of dominant-negative NF-YA reduced BRLF1 expression after radiation and cisplatin by 2.8-fold; in turn, overexpression of NF-YA resulted in a 2-fold increase in both BRLF1 and BZLF1 expression. Conclusions: These results show that NF-Y is an important mediator of EBV stress response in switching from a latent to lytic state. This novel insight could provide a potential therapeutic strategy to enhance NPC response to radiation and cisplatin.

show abstract

Section: Resultsmentioning

confidence: 99%

Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer

Chia

Leung

Krushel

et al. 2008

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…ChIP studies were performed as described elsewhere (Caretti et al, 2003) with antibodies FUS (H76), and DDIT3 (GADD153 R20) from Santa Cruz Biotechnology. Satellite FUS-DDIT3 deregulates NF-jB target genes M Göransson et al sequences repeated at multiple positions in the genome were used as a control for unspecific precipitation and as a loading control.…”

Section: Immunoprecipitation and Western Blotmentioning

confidence: 99%

The myxoid liposarcoma FUS-DDIT3 fusion oncoprotein deregulates NF-κB target genes by interaction with NFKBIZ

et al. 2008

View full text Add to dashboard Cite

FUS (also called TLS), EWSR1 and TAF15 (also called TAF2N) are related genes involved in tumor type-specific fusion oncogenes in human malignancies. The FUS-DDIT3 fusion oncogene results from a t(12;16)(q13;p11) chromosome translocation and has a causative role in the initiation of myxoid/round cell liposarcomas (MLS/ RCLS). The FUS-DDIT3 protein induces increased expression of the CAAT/enhancer-binding protein (C/EBP) and nuclear factor-jB (NF-jB)-controlled gene IL8, and the N-terminal FUS part is required for this activation. Chromatin immunoprecipitation analysis showed that FUS-DDIT3 binds the IL8 promoter. Expression studies of the IL8 promoter harboring a C/EBP-NF-jB composite site pinpointed the importance of NF-jB for IL8 expression in FUS-DDIT3-expressing cells. We therefore probed for possible interaction of FUS-DDIT3 with members of the NF-jB family. The nuclear factor NFKBIZ colocalizes with FUS-DDIT3 in nuclear structures, and immunoprecipitation experiments showed that FUS-DDIT3 binds the C-terminal of NFKBIZ. We also report that additional NF-jB-controlled genes are upregulated at the mRNA level in FUS-DDIT3-expressing cell lines and they can be induced by NFKBIZ. Taken together, the results indicate that FUS-DDIT3 deregulates some NF-jB-controlled genes through interactions with NFKBIZ. Similar mechanisms may be a part of the transformation process in other tumor types carrying FUS, EWSR1 and TAF15 containing fusion oncogenes.

show abstract

“…This mode of repression by Rb is in direct contrast to activation by E2F, which can bind to the histone acetylases (HATs) p300/CBP and P/CAF, making the DNA more accessible to transcription factors. RB/E2F-binding status, acetylation of E2F-dependent promoters and induction of transcription have been shown to be coordinated in a number of studies examining the proteins localized to the promoters of E2F-dependent genes at different stages of the cell cycle (Takahashi et al, 2000;Ferreira et al, 2001;Rayman et al, 2002;Caretti et al, 2003;Taubert et al, 2004). As compared to quiescent cells, in late G1 there is a loss of the pocket proteins and repressive E2Fs (E2F 4/p130), which are replaced by activating E2Fs.…”

Section: Mechanisms Of Transcriptional Controlmentioning

confidence: 99%