HIRA, a mammalian homologue of Saccharomyces cerevisiae transcriptional co-repressors, interacts with Pax3

Magnaghi, Paola; Roberts, Catherine; Lorain, Stéphanie; Lipinski, Marc; Scambler, Peter J.

doi:10.1038/1739

Cited by 129 publications

(93 citation statements)

References 26 publications

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“…These same two regions were also shown to have independent transcriptional repression activity when fused to the GAL4 DNA binding domain (Chalepakis et al, 1994b). Protein interaction studies subsequently determined that the putative co-repressors DAXX, RB1, and HIRA bind to PAX3, and for DAXX and HIRA, interactions with PAX7 were also noted Magnaghi et al, 1998;Wiggan et al, 1998). Deletion studies suggest that these proteins interact with the PAX3 homeodomain, though the DAXX interactions also appear to involve the octapeptide and other Nterminal regions.…”

Section: Transcriptional Properties Of Wild-type and Chimeric Pax Promentioning

confidence: 99%

Gene fusions involving PAX and FOX family members in alveolar rhabdomyosarcoma

2001

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The chromosomal translocations t(2;13)(q35;q14) and t(1;13)(p36;q14) are characteristic of alveolar rhabdomyosarcoma, a pediatric soft tissue cancer related to the striated muscle lineage. These translocations rearrange PAX3 and PAX7, members of the paired box transcription factor family, and juxtapose these genes with FKHR, a member of the fork head transcription factor family. This juxtaposition generates PAX3 ± FKHR and PAX7 ± FKHR chimeric genes that are expressed as chimeric transcripts that encode chimeric proteins. The fusion proteins, which contain the PAX3/PAX7 DNA binding domain and the FKHR transcriptional activation domain, activate transcription from PAX-binding sites with higher potency than the corresponding wild-type PAX proteins. This increased function results from the insensitivity of the FKHR activation domain to inhibitory e ects of N-terminal PAX3/PAX7 domains. In addition to altered function, the fusion products are expressed in ARMS tumors at higher levels than the corresponding wild-type PAX products due to two distinct mechanisms. The PAX7 ± FKHR fusion is overexpressed as a result of in vivo ampli®cation while the PAX3 ± FKHR fusion is overexpressed due to a copy number-independent increase in transcriptional rate. Finally, though FKHR subcellular localization is regulated by an AKTdependent pathway, the fusion proteins are resistant to these signals and show exclusively nuclear localization. Therefore, these translocations alter biological activity at the levels of protein function, gene expression, and subcellular localization with the cumulative outcome postulated to be aberrant regulation of PAX3/PAX7 target genes. This aberrant gene expression program is then hypothesized to contribute to tumorigenic behavior by impacting on the control of growth, apoptosis, di erentiation and motility. Oncogene (2001) 20, 5736 ± 5746.

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Section: Transcriptional Properties Of Wild-type and Chimeric Pax Promentioning

confidence: 99%

Gene fusions involving PAX and FOX family members in alveolar rhabdomyosarcoma

2001

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“…Both FOXD3 and PAX3 are known to physically interact with other transcription factors (Magnaghi et al, 1998;Wiggan et al, 1998;Hollenbach et al, 1999;Guo et al, 2002;Hollenbach et al, 2002). After observing that FOXD3 appears to prevent the binding of PAX3 to the MITF promoter, we wished to determine whether FOXD3 could physically interact with PAX3 in the absence of DNA.…”

Section: Research Articlementioning

confidence: 99%

“…This mechanism for inhibition of PAX3 function is not without precedent. PAX3 is known to interact with other transcription factors through its paired domain and homeodomain to either enhance (Lang and Epstein, 2003) or repress (Magnaghi et al, 1998;Wiggan et al, 1998;Hollenbach et al, 1999;Hollenbach et al, 2002) transcription. It is not yet known which domains of FOX3 and PAX3 are involved in their interaction.…”

Section: Mechanism Of Repressionmentioning

confidence: 99%

FOXD3 regulates the lineage switch between neural crest-derived glial cells and pigment cells by repressing MITF through a non-canonical mechanism

2009

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The first neural crest cells to emigrate from the neural tube are specified as neurons and glial cells and are subsequently followed by melanocytes of the skin. We wished to understand how this fate switch is controlled. The transcriptional repressor FOXD3 is expressed exclusively in the neural/glial precursors and MITF is expressed only in melanoblasts. Moreover, FOXD3 represses melanogenesis. Here we show that avian MITF expression begins very early during melanoblast migration and that loss of MITF in melanoblasts causes them to transdifferentiate to a glial phenotype. Ectopic expression of FOXD3 represses MITF in cultured neural crest cells and in B16-F10 melanoma cells. We also show that FOXD3 does not bind directly to the MITF promoter, but instead interacts with the transcriptional activator PAX3 to prevent the binding of PAX3 to the MITF promoter. Overexpression of PAX3 is sufficient to rescue MITF expression from FOXD3-mediated repression. We conclude that FOXD3 controls the lineage choice between neural/glial and pigment cells by repressing MITF during the early phase of neural crest migration.

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“…HIRA proteins are characterized by seven conserved WD repeats in their N-terminal, which are predicted to assemble into a b-propeller structure known to provide interfaces for protein-protein interactions (Komachi et al 1994;Smith et al 1999). The region C-terminal to the WD repeat domains is responsible for its binding ability as to homeodomains, Hir3p, Pax3, and core histones Magnaghi et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Identical sequences but different expression patterns of Hira gene in gynogenetic and gonochoristic crucian carps

Zhou

Zhao

et al. 2007

Fish Physiol Biochem

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Hir/Hira (histone regulation) genes were first identified in yeast as negative regulators of histone gene expression. It has been confirmed that HIRA is a conserved family of proteins present in various animals and plants. In this paper, the cDNAs of the Hira homolog named CagHira and CaHira were isolated from gynogenetic gibel carp (gynocarp) and gonochoristic color crucian carp (gonocarp) respectively. The full-length CagHira is 3,860 bp in length with an open reading frame (ORF) of 3,033 bp that encodes 1,011 amino acids, while the full-length CaHira is 3,748 bp in length and also has an ORF of 3,033 bp. The deduced amino acid sequences of both Hira homologs contain seven WD domains and show high identity with other HIRA family members. RT-PCR analyses revealed strong expression of Hira in the ovaries, whereas no expression was detected in the testes of either of the fishes. Hira transcription was not detected in the liver of gyno-carp, but a high level of Hira mRNA was observed in gono-carp. The temporal expression pattern showed that the Hira mRNA is consistently expressed during all embryonic development stages in gyno-carp. However, the abundance of CaHira mRNA significantly decreased (P < 0.05) shortly after fertilization and then increased again and remained stable from gastrula till hatching. The varying spatiotemporal expression patterns of Hira genes in gyno-carp and gono-carp may be associated with the differing reproductive modes used by these two closely related fishes. Our results suggest that Hira may play a role not only in the decondensation of sperm nucleus and the formation of pronucleus during fertilization, but also in gastrulation and the subsequent development of embryos.

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HIRA, a mammalian homologue of Saccharomyces cerevisiae transcriptional co-repressors, interacts with Pax3

Cited by 129 publications

References 26 publications

Gene fusions involving PAX and FOX family members in alveolar rhabdomyosarcoma

Gene fusions involving PAX and FOX family members in alveolar rhabdomyosarcoma

FOXD3 regulates the lineage switch between neural crest-derived glial cells and pigment cells by repressing MITF through a non-canonical mechanism

Identical sequences but different expression patterns of Hira gene in gynogenetic and gonochoristic crucian carps

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