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PARP-1 is a transcriptional rheostat of metabolic and bivalent genes during development.

ABSTRACT: PARP-1 participates in various cellular processes, including gene regulation. In Drosophila, PARP-1 mutants undergo developmental arrest during larval-to-pupal transition. In this study, we investigated PARP-1 binding and its transcriptional regulatory role at this stage. Our findings revealed that PARP-1 binds and represses active metabolic genes, including glycolytic genes, whereas activating low-expression developmental genes, including a subset of "bivalent" genes in third-instar larvae. These bivalent promoters, characterized by dual enrichment of low H3K4me3 and high H3K27me3, a unimodal H3K4me1 enrichment at the transcription start site (conserved in C. elegans and zebrafish), H2Av depletion, and high accessibility, may persist throughout development. In PARP-1 mutant third-instar larvae, metabolic genes typically down-regulated during the larval-to-pupal transition in response to reduced energy needs were repressed by PARP-1. Simultaneously, developmental and bivalent genes typically active at this stage were activated by PARP-1. In addition, glucose and ATP levels were significantly reduced in PARP-1 mutants, suggesting an imbalance in metabolic regulation. We propose that PARP-1 is essential for maintaining the delicate balance between metabolic and developmental gene expression programs to ensure proper developmental progression.

SUBMITTER: Bamgbose G

PROVIDER: S-EPMC10682175 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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PARP-1 is a transcriptional rheostat of metabolic and bivalent genes during development.

Bamgbose Gbolahan G Tulin Alexei A

Life science alliance 20231127 2

PARP-1 participates in various cellular processes, including gene regulation. In <i>Drosophila</i>, PARP-1 mutants undergo developmental arrest during larval-to-pupal transition. In this study, we investigated PARP-1 binding and its transcriptional regulatory role at this stage. Our findings revealed that PARP-1 binds and represses active metabolic genes, including glycolytic genes, whereas activating low-expression developmental genes, including a subset of "bivalent" genes in third-instar larv ...[more]

PMID: 38012002

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Project description:BackgroundOlive (Olea europaea L.) fruits contain numerous secondary metabolites, primarily phenolics, terpenes and sterols, some of which are particularly interesting for their nutraceutical properties. This study will attempt to provide further insight into the profile of olive phenolic compounds during fruit development and to identify the major genetic determinants of phenolic metabolism.ResultsThe concentration of the major phenolic compounds, such as oleuropein, demethyloleuropein, 3-4 DHPEA-EDA, ligstroside, tyrosol, hydroxytyrosol, verbascoside and lignans, were measured in the developing fruits of 12 olive cultivars. The content of these compounds varied significantly among the cultivars and decreased during fruit development and maturation, with some compounds showing specificity for certain cultivars. Thirty-five olive transcripts homologous to genes involved in the pathways of the main secondary metabolites were identified from the massive sequencing data of the olive fruit transcriptome or from cDNA-AFLP analysis. Their mRNA levels were determined using RT-qPCR analysis on fruits of high- and low-phenolic varieties (Coratina and Dolce d'Andria, respectively) during three different fruit developmental stages. A strong correlation was observed between phenolic compound concentrations and transcripts putatively involved in their biosynthesis, suggesting a transcriptional regulation of the corresponding pathways. OeDXS, OeGES, OeGE10H and OeADH, encoding putative 1-deoxy-D-xylulose-5-P synthase, geraniol synthase, geraniol 10-hydroxylase and arogenate dehydrogenase, respectively, were almost exclusively present at 45 days after flowering (DAF), suggesting that these compounds might play a key role in regulating secoiridoid accumulation during fruit development.ConclusionsMetabolic and transcriptional profiling led to the identification of some major players putatively involved in biosynthesis of secondary compounds in the olive tree. Our data represent the first step towards the functional characterisation of important genes for the determination of olive fruit quality.

Project description:Heat shock protein (HSP)-encoding genes (hsp), part of the highly conserved heat shock response (HSR), are known to be induced by thermal stress in several organisms. In Neurospora crassa, three hsp genes, hsp30, hsp70, and hsp80, have been characterized; however, the role of defined cis elements in their responses to discrete changes in temperature remains largely unexplored. To fill this gap, while also aiming to obtain a reliable fungal heat shock-inducible system, we analyzed different sections of each hsp promoter by assessing the expression of real-time transcriptional reporters. Whereas all three promoters and their resected versions were acutely induced by high temperatures, only hsp30 displayed a broad range of expression and high tunability, amply exceeding other inducible promoter systems existing in Neurospora, such as quinic acid- or light-inducible ones. As proof of concept, we employed one of these promoters to control the expression of clr-2, which encodes the master regulator of Neurospora cellulolytic capabilities. The resulting strain fails to grow on cellulose at 25°C, whereas it grows robustly if heat shock pulses are delivered daily. Additionally, we designed two hsp30 synthetic promoters and characterized them, as well as the native promoters, using a gradient of high temperatures, yielding a wide range of responses to thermal stimuli. Thus, Neurospora hsp30-based promoters represent a new set of modular elements that can be used as transcriptional rheostats to adjust the expression of a gene of interest or for the implementation of regulated circuitries for synthetic biology and biotechnological strategies. IMPORTANCE A timely and dynamic response to strong temperature fluctuations is paramount for organismal biology. At the same time, inducible promoters are a powerful tool for fungal biotechnological and synthetic biology endeavors. In this work, we analyzed the activity of several N. crassa heat shock protein (hsp) promoters at a wide range of temperatures, observing that hsp30 exhibits remarkable sensitivity and a dynamic range of expression as we charted the response of this promoter to subtle increases in temperature, and also as we built and analyzed synthetic promoters based on hsp30 cis elements. As proof of concept, we tested the ability of hsp30 to provide tight control of a central process, cellulose degradation. While this study provides an unprecedented description of the regulation of the N. crassa hsp genes, it also contributes a noteworthy addition to the molecular toolset of transcriptional controllers in filamentous fungi.

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PARP-1 is a transcriptional rheostat of metabolic and bivalent genes during development.

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PARP-1 is a transcriptional rheostat of metabolic and bivalent genes during development.

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