Project description:FoxA transcription factors play major roles in organ-specific gene expression. How FoxA proteins achieve specificity is unclear, given their broad expression patterns and requirements in multiple cell types. Here, we characterize Sage, a basic helix-loop-helix (bHLH) transcription factor expressed exclusively in the Drosophila salivary gland (SG). We identify Sage targets and show that not only are both Sage and the single Drosophila FoxA protein, Fork head (Fkh), required for expression of these genes, but coexpression of Sage and Fkh is sufficient to drive target gene expression in multiple other cell types. Sage and Fkh drive expression of the bZip transcription factor Senseless (Sens), which boosts expression of Sage/Fkh targets. Importantly, Sage, Fkh and Sens colocalize on salivary gland polytene chromosomes. Thus, Fkh drives cell-type specific gene expression as part of a tissue-specific transcription module that includes Sage and Sens, providing a new paradigm for how mammalian FoxA proteins acheive specificity.
Project description:FoxA transcription factors play major roles in organ-specific gene expression. How FoxA proteins achieve specificity is unclear, given their broad expression patterns and requirements in multiple cell types. Here, we characterize Sage, a basic helix-loop-helix (bHLH) transcription factor expressed exclusively in the Drosophila salivary gland (SG). We identify Sage targets and show that not only are both Sage and the single Drosophila FoxA protein, Fork head (Fkh), required for expression of these genes, but coexpression of Sage and Fkh is sufficient to drive target gene expression in multiple other cell types. Sage and Fkh drive expression of the bZip transcription factor Senseless (Sens), which boosts expression of Sage/Fkh targets. Importantly, Sage, Fkh and Sens colocalize on salivary gland polytene chromosomes. Thus, Fkh drives cell-type specific gene expression as part of a tissue-specific transcription module that includes Sage and Sens, providing a new paradigm for how mammalian FoxA proteins acheive specificity.
Project description:FoxA transcription factors play major roles in organ-specific gene expression. How FoxA proteins achieve specificity is unclear, given their broad expression patterns and requirements in multiple cell types. Here, we characterize Sage, a basic helix-loop-helix (bHLH) transcription factor expressed exclusively in the Drosophila salivary gland (SG). We identify Sage targets and show that not only are both Sage and the single Drosophila FoxA protein, Fork head (Fkh), required for expression of these genes, but coexpression of Sage and Fkh is sufficient to drive target gene expression in multiple other cell types. Sage and Fkh drive expression of the bZip transcription factor Senseless (Sens), which boosts expression of Sage/Fkh targets. Importantly, Sage, Fkh and Sens colocalize on salivary gland polytene chromosomes. Thus, Fkh drives cell-type specific gene expression as part of a tissue-specific transcription module that includes Sage and Sens, providing a new paradigm for how mammalian FoxA proteins acheive specificity. Three wild type (reference) samples were obtained from the Oregon R strain, age matched and treated the same as the three experimental samples isolated from Stages 11-16 embryos expressing UAS-Sage controlled by the tub-Gal4 driver.
Project description:FoxA transcription factors play major roles in organ-specific gene expression. How FoxA proteins achieve specificity is unclear, given their broad expression patterns and requirements in multiple cell types. Here, we characterize Sage, a basic helix-loop-helix (bHLH) transcription factor expressed exclusively in the Drosophila salivary gland (SG). We identify Sage targets and show that not only are both Sage and the single Drosophila FoxA protein, Fork head (Fkh), required for expression of these genes, but coexpression of Sage and Fkh is sufficient to drive target gene expression in multiple other cell types. Sage and Fkh drive expression of the bZip transcription factor Senseless (Sens), which boosts expression of Sage/Fkh targets. Importantly, Sage, Fkh and Sens colocalize on salivary gland polytene chromosomes. Thus, Fkh drives cell-type specific gene expression as part of a tissue-specific transcription module that includes Sage and Sens, providing a new paradigm for how mammalian FoxA proteins acheive specificity. Three control samples were obtained from the tub-Gal4 strain, age matched and treated the same as the three experimental samples isolated from Stages 11-16 embryos expressing UAS-Sage controlled by the tub-Gal4 driver.
Project description:FoxA transcription factors play major roles in organ-specific gene expression. How FoxA proteins achieve specificity is unclear, given their broad expression patterns and requirements in multiple cell types. Here, we characterize Sage, a basic helix-loop-helix (bHLH) transcription factor expressed exclusively in the Drosophila salivary gland (SG). We identify Sage targets and show that not only are both Sage and the single Drosophila FoxA protein, Fork head (Fkh), required for expression of these genes, but coexpression of Sage and Fkh is sufficient to drive target gene expression in multiple other cell types. Sage and Fkh drive expression of the bZip transcription factor Senseless (Sens), which boosts expression of Sage/Fkh targets. Importantly, Sage, Fkh and Sens colocalize on salivary gland polytene chromosomes. Thus, Fkh drives cell-type specific gene expression as part of a tissue-specific transcription module that includes Sage and Sens, providing a new paradigm for how mammalian FoxA proteins acheive specificity.
Project description:FoxA transcription factors play major roles in organ-specific gene expression. How FoxA proteins achieve specificity is unclear, given their broad expression patterns and requirements in multiple cell types. Here, we characterize Sage, a basic helix-loop-helix (bHLH) transcription factor expressed exclusively in the Drosophila salivary gland (SG). We identify Sage targets and show that not only are both Sage and the single Drosophila FoxA protein, Fork head (Fkh), required for expression of these genes, but coexpression of Sage and Fkh is sufficient to drive target gene expression in multiple other cell types. Sage and Fkh drive expression of the bZip transcription factor Senseless (Sens), which boosts expression of Sage/Fkh targets. Importantly, Sage, Fkh and Sens colocalize on salivary gland polytene chromosomes. Thus, Fkh drives cell-type specific gene expression as part of a tissue-specific transcription module that includes Sage and Sens, providing a new paradigm for how mammalian FoxA proteins acheive specificity. Three wild type (reference) samples were obtained from the Oregon R strain, age matched and treated the same as the three experimental samples isolated from Stages 11-16 sage mutant embryos.
Project description:Salivary gland-specific binding assays reveal that CrebA, a bZIP transcription factor, directly binds the vast majority of genes encoding the secretory machinery, including proteins of the signal recognition particle and receptor, proteins involved in co-translational import of cargo into the ER, proteins involved in vesicular transport between the ER and Golgi, as well as the structural proteins and enzymes of these organelles. CrebA does not bind salivary gland-specific cargo genes. Instead, it binds and boosts expression of Sage, which encodes a bHLH transcription factor that upregulates cargo expression. CrebA also directly binds and upregulates Xbp1, which encodes a key factor in the unfolded protein response, and Tudor-SN, which encodes a protein that in other systems increases secretory cargo mRNA levels.