The CrebA/Creb3-like transcription factors are major and direct regulators of secretory capacity
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-23346
PROVIDER: PRJNA131459 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Abstract: Secretion occurs in all cells, with relatively low levels in most cells and extremely high levels in specialized secretory cells, such as those of the pancreas, salivary and mammary glands. Here, we report that the CrebA/Creb3-like family of bZip transcription factors functions to upregulate expression of both the general protein machinery required in all cells for secretion and of cell-type specific secreted proteins. Drosophila CrebA directly binds the enhancers of secretory pathway genes and is both necessary and sufficient to activate expression of every secretory pathway component gene examined thus far. Microarray profiling reveals that CrebA also upregulates expression of genes encoding cell type specific secreted components. Finally, we find that the human CrebA orthologues, Creb3L1 and Creb3L2, have the ability to upregulate the secretory pathway in non-secretory cell types. This SuperSeries is composed of the following subset Series: GSE23334: Active Creb3L1 can upregulate secretory pathway genes in HeLa cells GSE23346: CrebA is a major and direct regulator of secretory pathway gene expression Refer to individual Series
2010-10-18 | E-GEOD-23349 | biostudies-arrayexpress
Project description:Abstract: Secretion occurs in all cells, with relatively low levels in most cells and extremely high levels in specialized secretory cells, such as those of the pancreas, salivary and mammary glands. Here, we report that the CrebA/Creb3-like family of bZip transcription factors functions to upregulate expression of both the general protein machinery required in all cells for secretion and of cell-type specific secreted proteins. Drosophila CrebA directly binds the enhancers of secretory pathway genes and is both necessary and sufficient to activate expression of every secretory pathway component gene examined thus far. Microarray profiling reveals that CrebA also upregulates expression of genes encoding cell type specific secreted components. Finally, we find that the human CrebA orthologues, Creb3L1 and Creb3L2, have the ability to upregulate the secretory pathway in non-secretory cell types. This SuperSeries is composed of the SubSeries listed below.
2010-10-18 | GSE23349 | GEO
Project description:Abstract: Secretion occurs in all cells, with relatively low levels in most cells and extremely high levels in specialized secretory cells, such as those of the pancreas, salivary and mammary glands. Here, we report that the CrebA/Creb3-like family of bZip transcription factors functions to upregulate expression of both the general protein machinery required in all cells for secretion and of cell-type specific secreted proteins. Drosophila CrebA directly binds the enhancers of secretory pathway genes and is both necessary and sufficient to activate expression of every secretory pathway component gene examined thus far. Microarray profiling reveals that CrebA also upregulates expression of genes encoding cell type specific secreted components. Finally, we find that the human CrebA orthologues, Creb3L1 and Creb3L2, have the ability to upregulate the secretory pathway in non-secretory cell types. Goals: The goals of the microarray experiments were to identify additional targets of the CrebA transcription factor to learn the range of genes regulated by this transcription factor during embryogenesis. Previous work had indicated that CrebA upregulates the protein machinery of the early secretory pathway. Our new data now shows that in addition to the protein machinery, CrebA also upregulates genes encoding the protein cargo that is secreted from specialized secretory organs. RNA was isolated from stage 11-15 wild type Drosophila embryos and compared to RNA from CrebA null mutant embryos of the same age; all samples were hybridized to the Drosophila Genome 2.0 Affymetrix array. Three individual replicates were obtained for each sample.
2010-10-18 | E-GEOD-23346 | biostudies-arrayexpress
Project description:Abstract: Secretion occurs in all cells, with relatively low levels in most cells and extremely high levels in specialized secretory cells, such as those of the pancreas, salivary and mammary glands. Here, we report that the CrebA/Creb3-like family of bZip transcription factors functions to upregulate expression of both the general protein machinery required in all cells for secretion and of cell-type specific secreted proteins. Drosophila CrebA directly binds the enhancers of secretory pathway genes and is both necessary and sufficient to activate expression of every secretory pathway component gene examined thus far. Microarray profiling reveals that CrebA also upregulates expression of genes encoding cell type specific secreted components. Finally, we find that the human CrebA orthologues, Creb3L1 and Creb3L2, have the ability to upregulate the secretory pathway in non-secretory cell types. Goals: The goals of the microarray experiments were to identify additional targets of the CrebA transcription factor to learn the range of genes regulated by this transcription factor during embryogenesis. Previous work had indicated that CrebA upregulates the protein machinery of the early secretory pathway. Our new data now shows that in addition to the protein machinery, CrebA also upregulates genes encoding the protein cargo that is secreted from specialized secretory organs.
2010-10-18 | GSE23346 | GEO
Project description:DNA binding assays, expression analyses, and binding site mutagenesis revealed that the Drosophila CrebA transcription factor (TF) boosts secretory capacity in the embryonic salivary gland (SG) through direct regulation of secretory pathway component genes (SPCGs). The mammalian orthologues of CrebA, the Creb3L-family of leucine zipper TFs, not only activate SPCG expression in a variety of mammalian tissues but can also activate SPCG expression in Drosophila embryos, suggesting a highly conserved role for this family of proteins in boosting secretory capacity. However, in vivo assays reveal that CrebA binds far more genes than it regulates, and it remains unclear what distinguishes functional binding. It is also unclear if CrebA is the major factor driving SPCG gene expression in all Drosophila embryonic tissues and/or if CrebA also regulates other tissue-specific functions. Thus, we did single cell RNA sequencing (scRNA-seq) of wild-type (WT) and CrebA null embryos to explore the relationship between CrebA binding and gene regulation. We find that CrebA binds the proximal promoters of its targets, that SPCGs are the major class of genes regulated by CrebA across tissues, and that CrebA is sufficient to activate SPCG expression even in cells that do not normally express the protein. A comparison of scRNA-Seq to other methods for capturing regulated transcripts reveals that the different methodologies identify overlapping but distinct sets of CrebA targets.
2025-10-01 | GSE306121 | GEO
Project description:Abstract: Secretion occurs in all cells, with relatively low levels in most cells and extremely high levels in specialized secretory cells, such as those of the pancreas, salivary and mammary glands. Here, we report that the CrebA/Creb3-like family of bZip transcription factors functions to upregulate expression of both the general protein machinery required in all cells for secretion and of cell-type specific secreted proteins. Drosophila CrebA directly binds the enhancers of secretory pathway genes and is both necessary and sufficient to activate expression of every secretory pathway component gene examined thus far. Microarray profiling reveals that CrebA also upregulates expression of genes encoding cell type specific secreted components. Finally, we find that the human CrebA orthologues, Creb3L1 and Creb3L2, have the ability to upregulate the secretory pathway in non-secretory cell types. Goals: Creb3L1 is the closest related human orthologue of Drosophila CrebA. CrebA is required to upregulate genes encoding the protein machinery and cargo in specialized secretory cells. To determine if the human orthologues of CrebA, Creb3L1 and Creb3L2, perform the same function, we expressed the truncated active form of Creb3L1 in non-secretory HeLa cells. We then performed microarray experiments and found that active Creb3L1 is sufficient to upregulate genes encoding the protein machinery of the secretory pathway, as observed with Drosophila CrebA. HeLa cells were transiently co-transfected with truncated Creb3L1 (Creb3L1 T) and GFP. Following 20 hours in culture, GFP positive cells were isolated by FACS and RNA was extracted using the Rneasy kit (Qiagen). As a control, mock transfected cells were also subjected to cell sorting and RNA was extracted using the same protocols. At least three replicates were obtained for each group.
2010-10-18 | E-GEOD-23334 | biostudies-arrayexpress
Project description:Abstract: Secretion occurs in all cells, with relatively low levels in most cells and extremely high levels in specialized secretory cells, such as those of the pancreas, salivary and mammary glands. Here, we report that the CrebA/Creb3-like family of bZip transcription factors functions to upregulate expression of both the general protein machinery required in all cells for secretion and of cell-type specific secreted proteins. Drosophila CrebA directly binds the enhancers of secretory pathway genes and is both necessary and sufficient to activate expression of every secretory pathway component gene examined thus far. Microarray profiling reveals that CrebA also upregulates expression of genes encoding cell type specific secreted components. Finally, we find that the human CrebA orthologues, Creb3L1 and Creb3L2, have the ability to upregulate the secretory pathway in non-secretory cell types. Goals: Creb3L1 is the closest related human orthologue of Drosophila CrebA. CrebA is required to upregulate genes encoding the protein machinery and cargo in specialized secretory cells. To determine if the human orthologues of CrebA, Creb3L1 and Creb3L2, perform the same function, we expressed the truncated active form of Creb3L1 in non-secretory HeLa cells. We then performed microarray experiments and found that active Creb3L1 is sufficient to upregulate genes encoding the protein machinery of the secretory pathway, as observed with Drosophila CrebA.
2010-10-18 | GSE23334 | GEO
Project description:Secretion occurs in all cells, with relatively low levels in most cells and extremely high levels in specialized secretory cells, such as those of the pancreas, salivary, and mammary glands. How secretory capacity is selectively up-regulated in specialized secretory cells is unknown. Here, we find that the CrebA/Creb3-like family of bZip transcription factors functions to up-regulate expression of both the general protein machinery required in all cells for secretion and of cell type-specific secreted proteins. Drosophila CrebA directly binds the enhancers of secretory pathway genes and is both necessary and sufficient to activate expression of every secretory pathway component gene examined thus far. Microarray profiling reveals that CrebA also up-regulates expression of genes encoding cell type-specific secreted components. Finally, we found that the human CrebA orthologues, Creb3L1 and Creb3L2, have the ability to up-regulate the secretory pathway in nonsecretory cell types.
| S-EPMC3003312 | biostudies-literature
Project description:CrebA regulation of secretory capacity: Genome-wide transcription profiling coupled with in vivo DNA binding studies
| PRJNA1309462 | ENA
Project description:Specialization of many cells, including the acinar cells of the salivary glands and pancreas, milk-producing cells of mammary glands, mucus-secreting goblet cells, antibody-producing plasma cells, and cells that generate the dense extracellular matrices of bone and cartilage, requires scaling up both secretory machinery and cell-type specific secretory cargo. Using tissue-specific genome-scale analyses, we determine how increases in secretory capacity are coordinated with increases in secretory load in the Drosophila salivary gland (SG), an ideal model for gaining mechanistic insight into the functional specialization of secretory organs. Our findings show that CrebA, a bZIP transcription factor, directly binds genes encoding the core secretory machinery, including protein components of the signal recognition particle and receptor, ER cargo translocators, Cop I and Cop II vesicles, as well as the structural proteins and enzymes of these organelles. CrebA directly binds a subset of SG cargo genes and CrebA binds and boosts expression of Sage, a SG-specific transcription factor essential for cargo expression. To further enhance secretory output, CrebA binds and activates Xbp1 and Tudor-SN. Thus, CrebA directly upregulates the machinery of secretion and additional factors to increase overall secretory capacity in professional secretory cells; concomitant increases in cargo are achieved both directly and indirectly.
| S-EPMC8142552 | biostudies-literature