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ABSTRACT: Genome-wide reprogramming of transcript architecture by temperature specifies the developmental states of the human pathogen Histoplasma

PROVIDER: PRJNA283424 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR2015210.fastq.gz	Fastqsanger.gz
	SRR2015220_1.fastq.gz	Fastqsanger.gz
	SRR2015220_2.fastq.gz	Fastqsanger.gz
	SRR2015230_1.fastq.gz	Fastqsanger.gz
	SRR2015230_2.fastq.gz	Fastqsanger.gz

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Project description:Genome-wide reprogramming of transcript architecture by temperature specifies the developmental states of the human pathogen Histoplasma [ribosome profiling]

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Genome-wide reprogramming of transcript architecture by temperature specifies the developmental states of the human pathogen Histoplasma [transcriptional profiling]

Project description:Eukaryotic cells integrate layers of gene regulation to coordinate complex cellular processes; however, mechanisms of post-transcriptional gene regulation remain poorly studied. The human fungal pathogen Histoplasma capsulatum (Hc) responds to environmental or host temperature by initiating unique transcriptional programs to specify multicellular (hyphae) or unicellular (yeast) developmental states that function in infectivity or pathogenesis, respectively. Here we used recent advances in next-generation sequencing to uncover a novel post-transcriptional mechanism of gene regulation in Hc developmental cell types. We found that ~2% percent of Hc transcripts exhibit 5’ leader sequences that differ markedly in length between morphogenetic states. Ribosome density and mRNA abundance measurements uncovered a class of differential leader transcripts that exhibit tight transcriptional and translational regulation. Further examination of these dually regulated genes revealed that some control Hc morphology and that their strict regulation is necessary for the pathogen to make appropriate developmental decisions in response to temperature. This series contains expression profiling data for four strains of Hc.

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The Rpd3 histone deacetylase is critical for temperature-mediated morphogenesis and virulence in the human fungal pathogen Histoplasma -- HDACi RNA-seq

Project description:Adaptive responses to environmental stimuli are integral to the survival and virulence of microbial pathogens. The thermally dimorphic human fungal pathogen Histoplasma senses temperature to transition between a mold form in soil and a pathogenic yeast in mammalian hosts. The contributions of chromatin-modifying enzymes to the ability of Histoplasma to appropriately respond to temperature have never been explored. Through chemical inhibition and genetics, we determined that the class I histone deacetylase (HDAC) RPD3 is required for normal Histoplasma yeast morphology at 37 ºC. Rpd3 regulated the expression of key morphology-specific genes, including critical virulence factors and transcription factors (TFs), was required for normal DNA-binding activity of yeast-promoting TFs, and influenced histone acetylation levels at the loci of putative pro-filamentation TFs. Furthermore, Rpd3 was required for virulence in a macrophage model of infection. Taken together, Rpd3 is a critical regulatory component that both activates the pathogenesis program and represses the filamentation program to enable thermal dimorphism in Histoplasma. This work uncovers the crucial role that chromatin regulation plays in temperature response of this ubiquitous pathogen.

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