title: Structure-Function Analysis of the Drosophila melanogaster Caudal Transcription Factor Provides Insights into Core Promoter-preferential Activation.
abstract: Regulation of RNA polymerase II transcription is critical for the proper development, differentiation, and growth of an organism. The RNA polymerase II core promoter is the ultimate target of a multitude of transcription factors that control transcription initiation. Core promoters encompass the RNA start site and consist of functional elements such as the TATA box, initiator, and downstream core promoter element (DPE), which confer specific properties to the core promoter. We have previously discovered that Drosophila Caudal, which is a master regulator of genes involved in development and differentiation, is a DPE-specific transcriptional activator. Here, we show that the mouse Caudal-related homeobox (Cdx) proteins (mCdx1, mCdx2, and mCdx4) are also preferential core promoter transcriptional activators. To elucidate the mechanism that enables Caudal to preferentially activate DPE transcription, we performed structure-function analysis. Using a systematic series of deletion mutants (all containing the intact DNA-binding homeodomain) we discovered that the C-terminal region of Caudal contributes to the preferential activation of the fushi tarazu (ftz) Caudal target gene. Furthermore, the region containing both the homeodomain and the C terminus of Caudal was sufficient to confer core promoter-preferential activation to the heterologous GAL4 DNA-binding domain. Importantly, we discovered that Drosophila CREB-binding protein (dCBP) is a co-activator for Caudal-regulated activation of ftz. Strikingly, dCBP conferred the ability to preferentially activate the DPE-dependent ftz reporter to mini-Caudal proteins that were unable to preferentially activate ftz transcription themselves. Taken together, it is the unique combination of dCBP and Caudal that enables the co-activation of ftz in a core promoter-preferential manner.
authors.affiliation: From The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel and.
authors.forename: Hila
authors.initials: H
authors.lastname: Shir-Shapira
authors.affiliation: From The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel and.
authors.forename: Julia
authors.initials: J
authors.lastname: Sharabany
authors.affiliation: From The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel and.
authors.forename: Matan
authors.initials: M
authors.lastname: Filderman
authors.affiliation: From The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel and.
authors.forename: Diana
authors.initials: D
authors.lastname: Ideses
authors.affiliation: From The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel and.
authors.forename: Avital
authors.initials: A
authors.lastname: Ovadia-Shochat
authors.affiliation: The Wenner-Gren Institute, Developmental Biology, Stockholm University, Arrhenius Laboratories E3, SE-106 91 Stockholm, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Mannervik
authors.affiliation: From The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel and tamar.gershon@biu.ac.il.
authors.forename: Tamar
authors.initials: T
authors.lastname: Juven-Gershon
mesh_terms: D000818:Animals; D000071616:CDX2 Transcription Factor; D050882:CREB-Binding Protein / Q000378:metabolism; D002460:Cell Line; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D051717:Fushi Tarazu Transcription Factors / Q000235:genetics; D017344:Genes, Insect; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D016385:TATA Box; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D000071616:CDX2 Transcription Factor; C491272:Cdx1 protein, mouse; C487514:Cdx2 protein, mouse; C084563:Cdx4 protein, mouse; D029721:Drosophila Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C084564:cad protein, Drosophila; C497169:ftz protein, Drosophila; D050882:CREB-Binding Protein
keywords: CBP; Caudal; DPE; Drosophila; RNA polymerase II; core promoter; developmental factor; fushi tarazu; gene expression; transcription regulation