Fusions Involving Paired Box and Fork Head Family Transcription Factors in the Pediatric Cancer Alveolar Rhabdomyosarcoma

1997 ◽  
pp. 113-129 ◽  
Author(s):  
F. G. Barr
Keyword(s):  
Transcription Factors ◽  
Pediatric Cancer ◽  
Alveolar Rhabdomyosarcoma ◽  
Fork Head

scholarly journals The PAXFOXO1s trigger fast trans-differentiation of chick embryonic neural cells into alveolar rhabdomyosarcoma with tissue invasive properties limited by S phase entry inhibition

2020 ◽  
Author(s):  
Gloria Gonzalez Curto ◽  
Audrey Der Vartanian ◽  
Youcef Frarma ◽  
Line Manceau ◽  
Lorenzo Baldi ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Alveolar Rhabdomyosarcoma ◽  
Neural Cells ◽  
Wild Type ◽  
In Ovo ◽  
Driver Genes ◽  
Chromosome Translocations ◽  
Neural Origin ◽  
Cell Cycle Inhibition

AbstractThe chromosome translocations generating PAX3FOXO1 and PAX7FOXO1 chimeric proteins are the primary hallmarks of the paediatric cancer, Alveolar Rhabdomyosarcoma (ARMS). Despite the ability of these transcription factors to remodel chromatin landscapes and promote the expression of tumour driver genes, they only inefficiently promote malignant transformation in vivo. The reason for this is unclear. To address this, we developed an in ovo model to follow the response of spinal cord progenitors to PAXFOXO1s. Our data demonstrate that PAXFOXO1s, but not wild-type PAX3 and PAX7, trigger the trans-differentiation of neural cells into ARMS-like cells with myogenic characteristics. In parallel expression of PAXFOXO1s remodels the neural pseudo-stratified epithelium into a cohesive mesenchyme capable of tissue invasion. Surprisingly, gain for PAXFOXO1s, as for wild-type PAX3/7, reduces the levels of CDK-CYCLIN activity and arrests cells in G1. Introduction of CYCLIN D1 or MYCN overcomes PAXFOXO1s mediated cell cycle inhibition and promotes tumour growth. Together, our findings reveal a mechanism underpinning the apparent limited oncogenicity of PAXFOXO1 fusion transcription factors and support a neural origin for ARMS.

PES-1 is expressed during early embryogenesis in Caenorhabditis elegans and has homology to the fork head family of transcription factors

Development ◽  
1994 ◽  
Vol 120 (3) ◽  
pp. 505-514 ◽  
Author(s):  
I.A. Hope
Keyword(s):  
Transcription Factors ◽  
Caenorhabditis Elegans ◽  
Cell Lineage ◽  
Embryonic Cell ◽  
Early Embryogenesis ◽  
C Elegans ◽  
Promoter Trapping ◽  
Fork Head ◽  
Initiation Of Transcription ◽  
Beta Galactosidase

Promoter trapping has identified a gene, pes-1, which is expressed during C. elegans embryogenesis. The beta-galactosidase expression pattern, directed by the pes-1/lacZ fusion through which this gene was cloned, has been determined precisely in terms of the embryonic cell lineage and has three components. One component is in a subset of cells of the AB founder cell lineage during early embryogenesis, suggesting pes-1 may be regulated both by cell autonomous determinants and by intercellular signals. Analysis of cDNA suggests pes-1 has two sites for initiation of transcription and the two transcripts would encode related but distinct proteins. The predicted PES-1 proteins have homology to the fork head family of transcription factors and therefore may have important regulatory roles in early embryogenesis.

Characterization of the human lipoprotein lipase (LPL) promoter: evidence of two cis-regulatory regions, LP-alpha and LP-beta, of importance for the differentiation-linked induction of the LPL gene during adipogenesis

1992 ◽  
Vol 12 (10) ◽  
pp. 4622-4633 ◽  
Author(s):  
S Enerbäck ◽  
B G Ohlsson ◽  
L Samuelsson ◽  
G Bjursell
Keyword(s):  
Transcription Factors ◽  
Lipoprotein Lipase ◽  
Reporter Gene ◽  
Adipocyte Differentiation ◽  
Dnase I ◽  
Striking Similarity ◽  
Fork Head ◽  
Lpl Gene ◽  
Adipocyte Development

When preadipocytes differentiate into adipocytes, several differentiation-linked genes are activated. Lipoprotein lipase (LPL) is one of the first genes induced during this process. To investigate early events in adipocyte development, we have focused on the transcriptional activation of the LPL gene. For this purpose, we have cloned and fused different parts of intragenic and flanking sequences with a chloramphenicol acetyltransferase reporter gene. Transient transfection experiments and DNase I hypersensitivity assays indicate that several positive as well as negative elements contribute to transcriptional regulation of the LPL gene. When reporter gene constructs were stably introduced into preadipocytes, we were able to monitor and compare the activation patterns of different promoter deletion mutants at selected time points representing the process of adipocyte development. We could delimit two cis-regulatory elements important for gradual activation of the LPL gene during adipocyte development in vitro. These elements, LP-alpha (-702 to -666) and LP-beta (-468 to -430), contain a striking similarity to a consensus sequence known to bind the transcription factors HNF-3 and fork head. Results of gel mobility shift assays and DNase I and exonuclease III in vitro protection assays indicate that factors with DNA-binding properties similar to those of the HNF-3/fork head family of transcription factors are present in adipocytes and interact with LP-alpha and LP-beta. We also demonstrate that LP-alpha and LP-beta were both capable of conferring a differentiation-linked expression pattern to a heterolog promoter, thus mimicking the expression of the endogenous LPL gene during adipocyte differentiation. These findings indicate that interactions with LP-alpha and LP-beta could be a part of a differentiation switch governing induction of the LPL gene during adipocyte differentiation.

Target Site Determination for Xenopus Laevis Fork Head Related Transcription Factors

1995 ◽  
pp. 79-92
Author(s):  
Eckhard Kaufmann ◽  
Dorothée Müller ◽  
Petra Dege ◽  
Heiko Rauer ◽  
Heike Rohm ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Xenopus Laevis ◽  
Target Site ◽  
Fork Head

Murine chromosomal location of eight members of the hepatocyte nuclear factor 3/fork head winged helix family of transcription factors

Genomics ◽  
1995 ◽  
Vol 25 (2) ◽  
pp. 388-393 ◽  
Author(s):  
Karen B. Avraham ◽  
Colin Fletcher ◽  
David G. Overdier ◽  
Derek E. Clevidence ◽  
Eseng Lai ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Chromosomal Location ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Winged Helix ◽  
Fork Head

scholarly journals Overproduction of a truncated hepatocyte nuclear factor 3 protein inhibits expression of liver-specific genes in hepatoma cells.

1995 ◽  
Vol 15 (10) ◽  
pp. 5453-5460 ◽  
Author(s):  
V Vallet ◽  
B Antoine ◽  
P Chafey ◽  
A Vandewalle ◽  
A Kahn
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Binding Sites ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Hepatoma Cells ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Regulatory Regions ◽  
Truncated Protein ◽  
Fork Head

Transcription of hepatocyte-specific genes requires the interaction of their regulatory regions with several nuclear factors. Among them is the hepatocyte nuclear factor 3 (HNF3) family, composed of the HNF3 alpha, HNF3 beta, and HNF3 gamma proteins, which are expressed in the liver and have very similar fork head DNA binding domains. The regulatory regions of numerous hepatocyte-specific genes contain HNF3 binding sites. We examined the role of HNF3 proteins in the liver-specific phenotype by turning off the HNF3 activity in well-differentiated mhAT3F hepatoma cells. Cells were stably transfected with a vector allowing the synthesis of an HNF3 beta fragment consisting of the fork head DNA binding domain without the transactivating amino- and carboxy-terminal domains. The truncated protein was located in the nuclei of cultured hepatoma cells and competed with endogenous HNF3 proteins for binding to cognate DNA sites. Overproduction of this truncated protein, lacking any transactivating activity, induced a dramatic decrease in the expression of liver-specific genes, including those for albumin, transthyretin, transferrin, phosphoenolpyruvate carboxykinase, and aldolase B, whereas the expression of the L-type pyruvate kinase gene, containing no HNF3 binding sites, was unaltered. Neither were the concentrations of various liver-specific transcription factors (HNF3, HNF1, HNF4, and C/EBP alpha) affected. In partial revertants, with a lower ratio of truncated to full-length endogenous HNF3 proteins, previously extinguished genes were re-expressed. Thus, the transactivating domains of HNF3 proteins are needed for the proper expression of a set of liver-specific genes but not for expression of the genes encoding transcription factors found in differentiated hepatocytes.

Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma

1993 ◽  
Vol 5 (3) ◽  
pp. 230-235 ◽  
Author(s):  
Naomi Galili ◽  
Richard J. Davis ◽  
William J. Fredericks ◽  
Sunil Mukhopadhyay ◽  
Frank J. Rauscher ◽  
...  
Keyword(s):  
Solid Tumour ◽  
Alveolar Rhabdomyosarcoma ◽  
Fork Head ◽  
Head Domain

The binding of fork head proteins to DNA is partly determined by cooperation of bases

2006 ◽  
Vol 1 (4) ◽  
pp. 594-608
Author(s):  
Václav Mach
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Binding Sites ◽  
In Silico ◽  
Dna Recognition ◽  
Simple Algorithm ◽  
Fork Head ◽  
Statistical Algorithm ◽  
On Line ◽  
Negative Base

AbstractOur previous study revealed that DNA recognition by the insect Fork head transcription factors depends on specific combinations of neighboring bases, a phenomenon called the base cooperation effect. This study presents a simple algorithm designed for in silico investigation of the base cooperation effect. The algorithm measures and evaluates observed and expected frequencies of various base combinations within a set of aligned binding sites. Consequently, statistically significant differences between the observed and expected frequencies are interpreted as evidence of either positive or negative base cooperation effect. Our current results suggest that the base cooperation affects DNA binding of the vertebrate members of the Fork head family, similarly to their insect homologies.The statistical algorithm used in this study is available on line (http://blast.entu.cas.cz/bias/index.htm).

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