DNA binding preferences of fungal SREBP transcription regulators
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ABSTRACT:
PROVIDER: PRJNA485525 | ENA |
REPOSITORIES: ENA
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Project description:Goal: We employed ChIP-seq to identify direct targets of regulation of the Candida albicans SREBP transcription regulator Cph2.
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Project description:Candida albicans SREBP transcription regulators
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Project description:Goal: We employed RNA-seq to identify targets of regulation of the Candida albicans SREBP transcription regulators Cph2 and Hms1.
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Project description:Identifying regulatory network governed by Candida albicans SREBP transcription regulators
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Project description:Sterol regulatory element binding proteins (SREBPs) are key transcriptional regulators of lipid metabolism. To define functional differences between the three mammalian SREBPs we are using genome-wide ChIP-seq with isoform-specific antibodies and chromatin from select tissues of mice challenged with different dietary conditions that enrich for specific SREBPs. We show hepatic SREBP-2 binds preferentially to two different gene-proximal motifs. Gene ontology analyses suggests SREBP-2 targets lipid metabolic processes as expected but apoptosis and autophagy gene categories were also enriched. We show SREBP-2 directly activates autophagy genes during cell sterol depletion, conditions known to induce both autophagy and nuclear SREBP-2 levels. Additionally, SREBP-2 knockdown during nutrient depletion decreased autophagosome formation and lipid droplet association of the autophagosome targeting protein LC3. Thus, the lipid droplet could be viewed as a third source of cellular cholesterol, which along with sterol synthesis and uptake, is also regulated by SREBP-2. Examination of hepatic SREBP-2 binding using ChIP-Seq. One ChIP-Seq dataset and one IgG control.
2011-03-22 | E-GEOD-28082 | biostudies-arrayexpress
Project description:Sterol regulatory element binding proteins (SREBPs) are key transcriptional regulators of lipid metabolism. To define functional differences between the three mammalian SREBPs we are using genome-wide ChIP-seq with isoform-specific antibodies and chromatin from select tissues of mice challenged with different dietary conditions that enrich for specific SREBPs. We show hepatic SREBP-2 binds preferentially to two different gene-proximal motifs. Gene ontology analyses suggests SREBP-2 targets lipid metabolic processes as expected but apoptosis and autophagy gene categories were also enriched. We show SREBP-2 directly activates autophagy genes during cell sterol depletion, conditions known to induce both autophagy and nuclear SREBP-2 levels. Additionally, SREBP-2 knockdown during nutrient depletion decreased autophagosome formation and lipid droplet association of the autophagosome targeting protein LC3. Thus, the lipid droplet could be viewed as a third source of cellular cholesterol, which along with sterol synthesis and uptake, is also regulated by SREBP-2.
2011-03-23 | GSE28082 | GEO
Project description:Fine-tuning of lipogenic gene expression is important for the maintenance of long-term homeostasis of intracellular lipids. The SREBP family of transcription factors are master regulators that control the transcription of lipogenic and cholesterogenic genes, but the mechanisms modulating SREBP-dependent transcription are still not fully understood. We previously reported that CDK8, a subunit of the transcription co-factor Mediator complex, phosphorylates SREBP at a conserved threonine residue. Here, using Drosophila as a model system, we observed that the phosphodeficient SREBP proteins (SREBP-Thr390Ala) were more stable and more potent in stimulating the expression of lipogenic genes and promoting lipogenesis in vivo than wild-type SREBP. In addition, starvation blocked the effects of wild-type SREBP-induced lipogenic gene transcription, whereas phosphodeficient SREBP was resistant to this effect. Furthermore, our biochemical analyses identified six highly conserved amino acid residues in the N-terminus disordered region of SREBP that are required for its interactions with both Cdk8 and the MED15 subunit of the small Mediator complex. These results support that the concerted actions of Cdk8 and MED15 are essential for the tight regulation of SREBP-dependent transcription.
2022-11-09 | GSE217104 | GEO
Project description:All but a few eukaryotes die without oxygen and respond dynamically to changes in the level of oxygen available to them. One ancient oxygen-requiring biochemical pathway in eukaryotes is the pathway for the biosynthesis of sterols, leading to cholesterol in animals and ergosterol in fungi. Mutations in this pathway are a frequent cause of azole drug resistance in pathogenic fungi. The regulatory mechanism for the sterol pathway is also widely conserved between animals and fungi and is centred on a transcription activator, SREBP, that forms part of a sterol-sensing complex. However, in one group of yeasts – the Saccharomycotina, which includes the major pathogen Candida albicans – control of the sterol pathway has been taken over by an unrelated regulatory protein, Upc2. We show here by analysis of the yeast Yarrowia lipolytica that the evolutionary switch from SREBP to Upc2 was a two-step process in which Upc2 appeared in an ancestor of Saccharomycotina, and SREBP subsequently degenerated and lost its sterol-regulatory function while retaining an ancient role in filamentation.
2013-11-19 | GSE47433 | GEO
Project description:All but a few eukaryotes die without oxygen and respond dynamically to changes in the level of oxygen available to them. One ancient oxygen-requiring biochemical pathway in eukaryotes is the pathway for the biosynthesis of sterols, leading to cholesterol in animals and ergosterol in fungi. Mutations in this pathway are a frequent cause of azole drug resistance in pathogenic fungi. The regulatory mechanism for the sterol pathway is also widely conserved between animals and fungi and is centred on a transcription activator, SREBP, that forms part of a sterol-sensing complex. However, in one group of yeasts M-bM-^@M-^S the Saccharomycotina, which includes the major pathogen Candida albicans M-bM-^@M-^S control of the sterol pathway has been taken over by an unrelated regulatory protein, Upc2. We show here by analysis of the yeast Yarrowia lipolytica that the evolutionary switch from SREBP to Upc2 was a two-step process in which Upc2 appeared in an ancestor of Saccharomycotina, and SREBP subsequently degenerated and lost its sterol-regulatory function while retaining an ancient role in filamentation. RNA was isolated from Y. lipolytica wildtype (JMY2900) in normoxia (21% oxygen, 4 biological replicates), wildtype (JMY2900) in hypoxia (1% oxygen, 5 biological replicates), upc2 deletion (SMY2) in hypoxia (1% oxygen, 3 biological replicates), and from sre1 (SMY5, SMY8) deletion in hypoxia (1% oxygen, 2 biological replicates). Gene expression was determined using strand-specific RNA-seq.
2013-11-19 | E-GEOD-47433 | biostudies-arrayexpress
Project description:The Aspergillus fumigatus sterol regulatory element binding protein (SREBP) SrbA belongs to the basic Helix-Loop-Helix (bHLH) family of transcription factors and is crucial for antifungal drug resistance and virulence. The latter phenotype is especially striking, as loss of SrbA results in complete loss of virulence in murine models of invasive pulmonary aspergillosis (IPA). How fungal SREBPs mediate fungal virulence is unknown, though it has been suggested that lack of growth in hypoxic conditions accounts for the attenuated virulence. To further understand the role of SrbA in fungal infection site pathobiology, chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) was used to identify genes under direct SrbA transcriptional regulation in hypoxia. These results confirmed the direct regulation of ergosterol biosynthesis and iron uptake by SrbA in hypoxia and revealed new roles for SrbA in nitrate assimilation and heme biosynthesis. Moreover, functional characterization of an SrbA target gene with sequence similarity to SrbA identified a new transcriptional regulator of the fungal hypoxia response and virulence, SrbB. SrbB co-regulates genes involved in heme biosynthesis and demethylation of C4 sterols with SrbA in hypoxic conditions. However, SrbB also has regulatory functions independent of SrbA including regulation of carbohydrate metabolism. Loss of SrbB markedly attenuates A. fumigatus virulence, and loss of both SREBPs further reduces in vivo fungal growth. These data suggest that both A. fumigatus SREBPs are critical for hypoxia adaptation and virulence and reveals new insights into SREBPM-bM-^@M-^Ys complex role in infection site adaptation and fungal virulence. 4 hour and 12 hour ChIP experiments were completed. Input control samples for each set were collected.
2014-10-03 | E-GEOD-61974 | biostudies-arrayexpress