Identification of a new class of PAX3-FKHR target promoters: a role of the Pax3 paired box DNA binding domain.

Identification of a new class of PAX3-FKHR target promoters: a role of the Pax3 paired box DNA binding domain. Research Abstract Details 

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Identification of a new class of PAX3-FKHR target promoters: a role of the Pax3 paired box DNA binding domain. Abstract Text:

L Zhang,C Wang,L Zhang,C Wang,

Alveolar rhabdomyosarcoma (aRMS), an aggressive skeletal muscle cancer, carries a unique t(2;13) chromosomal translocation resulting in the formation of a chimeric transcription factor PAX3-FKHR. This fusion protein contains the intact DNA-binding domains (PD: paired box binding domain; HD: paired-type homeodomain) of Pax3 fused to the activation domain of FKHR. Cells expressing Pax3 and PAX3-FKHR show vastly different gene expression patterns, despite that they share the same DNA-binding domains. We present evidence of a gain of function mechanism that allows the fusion protein to recognize and transcriptionally activate response elements containing a PD-specific binding site. This DNA recognition specificity is in contrast to the requirement for Pax3-specific target sequences that must contain a composite of PD-and HD-binding sites. Domain swapping studies suggest that an increased structural flexibility could account for the relaxed DNA targeting specificity in PAX3-FKHR. Here, we identify myogenin gene as a direct target of PD-dependent PAX3-FKHR activation pathway in vitro and in vivo. We demonstrate that PAX3-FKHR could induce myogenin expression in undifferentiated myoblasts by a MyoD independent pathway, and that PAX3-FKHR is directly involved in myogenin expression in aRMS cells.

Identification of a new class of PAX3-FKHR target promoters: a role of the Pax3 paired box DNA binding domain. Publishing Authors By Initials

L Zhang,C Wang,L Zhang,C Wang,

For similar genetic processes: gene expression: transcription, genetic research abstracts see: genetic processes: gene expression: transcription, genetic research

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Identification of a new class of PAX3-FKHR target promoters: a role of the Pax3 paired box DNA binding domain. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Oncogene

VOLUME: 26

Page Numbers: 1595-605

Journal Abbreviation: Oncogene

ISSN: 0950-9232

DAY: 11

MONTH: 09

YEAR: 2006

Identification of a new class of PAX3-FKHR target promoters: a role of the Pax3 paired box DNA binding domain. Information

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LANGUAGE: eng

NlmUniqueID: 8711562

Identification of a new class of PAX3-FKHR target promoters: a role of the Pax3 paired box DNA binding domain. Keywords Mesh Terms:

KEYWORDS: Transcription, Genetic

MESH TERMS: genetics

Chemical & Substance for Abstract: Identification of a new class of PAX3-FKHR target promoters: a role of the Pax3 paired box DNA binding domain. Information

Substance Name: DNA

Registry Number: 9007-49-2

Grant and Affiliation Information for Identification of a new class of PAX3-FKHR target promoters: a role of the Pax3 paired box DNA binding domain.

AFFILIATION: Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Chicago, IL 60612, USA.

Country: England

AGENCY: United States NCI

GRANT: CA074907

ACRONYM: CA

MEDLINETA: Oncogene

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