The Hox Transcription Factor Ubx stabilizes Lineage Commitment by Suppressing Cellular Plasticity [RNA-seq]
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PROVIDER: PRJNA498087 | ENA |
REPOSITORIES: ENA
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Project description:The Hox Transcription Factor Ubx stabilizes Lineage Commitment by Suppressing Cellular Plasticity
| PRJNA498317 | ENA
Project description:During development cells become gradually restricted in their differentiation potential by the repression of alternative cell fates. While we know that the Polycomb complex plays a crucial role in this process, it still remains unclear how alternative fate genes are specifically targeted for silencing in different cell lineages. We address this question by studying Ultrabithorax (Ubx), a multi-lineage transcription factor (TF) of the Hox class, in the mesodermal and neuronal lineages using sorted nuclei of Drosophila embryos and by interfering with Ubx in mesodermal cells that have already initiated differentiation. We find that Ubx is a key regulator of lineage development, as its mesoderm-specific depletion leads to the de-repression of many genes normally expressed in other lineages. Ubx silences expression of alternative fate genes by interacting with and retaining the Polycomb Group (PcG) protein Pleiohomeotic (Pho) at Ubx targeted genomic regions, thereby setting repressive chromatin marks in a lineage-dependent manner. In sum, our study demonstrates that Ubx stabilizes lineage choice by suppressing the multi-potency encoded in the genome in a lineage-specific manner via its interaction with Pho. This mechanism may explain why the Hox code is maintained throughout the lifecycle, since it seems to set a block to transdifferentiation in many adult cells.
2019-05-04 | GSE121670 | GEO
Project description:During development cells become gradually restricted in their differentiation potential by the repression of alternative cell fates. While we know that the Polycomb complex plays a crucial role in this process, it still remains unclear how alternative fate genes are specifically targeted for silencing in different cell lineages. We address this question by studying Ultrabithorax (Ubx), a multi-lineage transcription factor (TF) of the Hox class, in the mesodermal and neuronal lineages using sorted nuclei of Drosophila embryos and by interfering with Ubx in mesodermal cells that have already initiated differentiation. We find that Ubx is a key regulator of lineage development, as its mesoderm-specific depletion leads to the de-repression of many genes normally expressed in other lineages. Ubx silences expression of alternative fate genes by interacting with and retaining the Polycomb Group (PcG) protein Pleiohomeotic (Pho) at Ubx targeted genomic regions, thereby setting repressive chromatin marks in a lineage-dependent manner. In sum, our study demonstrates that Ubx stabilizes lineage choice by suppressing the multi-potency encoded in the genome in a lineage-specific manner via its interaction with Pho. This mechanism may explain why the Hox code is maintained throughout the lifecycle, since it seems to set a block to transdifferentiation in many adult cells.
2019-05-02 | GSE121752 | GEO
Project description:The Hox Transcription Factor Ubx stabilizes Lineage Commitment by Suppressing Cellular Plasticity [ChIP-seq]
| PRJNA498315 | ENA
Project description: Not available
| S-EPMC6513553 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-05-02 | GSE121754 | GEO
Project description:Hox genes encode a family of transcription factors that are key developmental regulators with a highly conserved role in specifying segmental diversity along the metazoan body axis. Although they have been shown to regulate a wide variety of downstream processes, direct transcriptional targets have been difficult to identify and this has been a major obstacle to our understanding of Hox gene function. Here we report the use of a YFP-tagged Drosophila protein-trap line together with chromatin immunoprecipitation and microarray analysis to identify genome-wide binding sites for the Hox protein Ultrabithorax (Ubx). We find 1,147 genes bound by Ubx in chromatin from the haltere imaginal disc, a prominent site of Ubx function where it specifies haltere versus wing development. The functional relevance of these genes is supported by their overlap with genes showing differential expression between wing and haltere imaginal discs. The Ubx-bound genes are highly enriched in genes involved in developmental processes. They contain both high-level regulatory genes as well as genes involved in more basic cell functions supporting the idea that Hox genes regulate many levels of developmental pathways. Several signalling pathways are highly enriched and within these pathways Ubx target genes occur at multiple level from ligands to transcriptional effectors. We also performed genome-wide analysis of the binding sites for the Hox cofactor Homothorax (Hth), revealing a striking similarity in the binding profiles of Hth and Ubx. We suggest that these binding profiles may be strongly influenced by chromatin accessibility and we provide evidence of a clear link between Ubx/Hth binding and the chromatin state at genes regulated by Polycomb silencing. The role of chromatin accessibility has important implications for Hox gene function and for genomic target selection by transcription factors in general.
2011-04-14 | GSE23864 | GEO
Project description:Regulation of specific target genes by transcription factors is central to gene network control in development. How target specificity is achieved in eukaryotic genomes is poorly understood, as exemplified by the Hox family, which show limited in vitro DNA-binding specificity but clear functional specificity in vivo. We generated genome-wide binding profiles for three Hox proteins, Ubx, Abd-A and Abd-B, in Drosophila Kc167 cells, revealing clear target specificity and a striking influence of chromatin accessibility. Ubx and Abd-A bind to similar target sites in accessible chromatin whereas Abd-B binds additional specific targets. Provision of the TALE class cofactors, Exd and Hth, alters the Ubx binding profile, enabling binding to additional targets in the genome. Both the Abd-B specific targets and the cofactor-dependent Ubx targets are in relatively DNase1 inaccessible chromatin, suggesting that competition with nucleosomes is a key factor determining Hox protein target specificity. This ChIP-Seq study performed on Kc167 cells involves two experiments and 6 ChIP samples. In Experiment 1, we generated genome-wide binding profiles for Ubx, Abd-A and Abd-B. An equal volume of input chromatin was retained from each of the Hox samples and combined to represent the input, which was purified alongside the ChIP samples. We performed two biological replicates for each sample. Sequencing was performed using the Illumina MiSeq platform. In Experiment 2, we generated genome-wide binding profiles for Ubx, mutant Ubx and Ubx in the presence of Hth. We performed two biological replicates for each sample except Ubx where we performed just one. Sequencing was performed using the Illumina HiSeq 2000 platform. For all samples, Experiment 1 input chromatin was used as the reference control to assay ChIP enrichment.
2015-12-07 | E-GEOD-69796 | biostudies-arrayexpress
Project description:Regulation of specific target genes by transcription factors is central to gene network control in development. How target specificity is achieved in eukaryotic genomes is poorly understood, as exemplified by the Hox family, which show limited in vitro DNA-binding specificity but clear functional specificity in vivo. We generated genome-wide binding profiles for three Hox proteins, Ubx, Abd-A and Abd-B, in Drosophila Kc167 cells, revealing clear target specificity and a striking influence of chromatin accessibility. Ubx and Abd-A bind to similar target sites in accessible chromatin whereas Abd-B binds additional specific targets. Provision of the TALE class cofactors, Exd and Hth, alters the Ubx binding profile, enabling binding to additional targets in the genome. Both the Abd-B specific targets and the cofactor-dependent Ubx targets are in relatively DNase1 inaccessible chromatin, suggesting that competition with nucleosomes is a key factor determining Hox protein target specificity.
2015-12-07 | GSE69796 | GEO
Project description:Hox genes regionalize the animal body axis by modifying complex morphogenetic and differentiation processes during development. The transformation of wings into halteres by the Hox gene Ultrabithorax (Ubx) in Drosophila melanogaster presents an excellent model system to study the transcriptional networks that control such complex developmental programmes. We have employed an inducible misexpression system to switch on Ubx in the wing epithelium at successive larval, prepupal and pupal stages, and have used microarray expression profiling to identify the primary transcriptional responses to Ubx. We find that Ubx regulates hundreds of downstream genes, mostly in a subtle manner. These targets are largely distinct at the different stages of appendage development and diversification.
2010-12-31 | GSE22354 | GEO