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The Hippo Pathway Prevents YAP/TAZ–Driven Hypertranscription and Controls Neural Progenitor Number [ChIP-seq]

ABSTRACT: The Hippo Pathway Prevents YAP/TAZ–Driven Hypertranscription and Controls Neural Progenitor Number [ChIP-seq]

PROVIDER: PRJNA491363 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7850862.fastq.gz	Fastqsanger.gz
	SRR7850863.fastq.gz	Fastqsanger.gz
	SRR7850864.fastq.gz	Fastqsanger.gz
	SRR7850865.fastq.gz	Fastqsanger.gz
	SRR7850866.fastq.gz	Fastqsanger.gz

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The Hippo Pathway Prevents YAP/TAZ–Driven Hypertranscription and Controls Neural Progenitor Number [microarray]

Project description:The Hippo pathway controls the activity of YAP/TAZ transcriptional coactivators through a kinase cascade. Despite the critical role of this pathway in tissue growth and tumorigenesis, it is not fully understood how YAP/TAZ–mediated transcription drives proliferation. By analyzing the effects of inactivating LATS1/2 kinases, the direct upstream inhibitors of YAP/TAZ, on mouse brain development and applying cell-number–normalized transcriptome analysis, we discovered that YAP/TAZ activation causes a global increase in transcription activity, known as hypertranscription, and upregulates many genes associated with increased biosynthetic capacity and proliferation. In contrast, conventional read-depth–normalized RNA-sequencing analysis failed to detect the scope of the transcriptome shift and missed most relevant gene ontologies. Hypertranscription in neural progenitors inhibits differentiation and triggers DNA replication stress, DNA damage, and p53 activation, resulting in massive apoptosis. Our findings reveal the remarkable impact of YAP/TAZ activation on global transcription activity and have important implications for understanding YAP/TAZ function

2019-02-19 | GSE119935 | GEO

The Hippo Pathway Prevents YAP/TAZ–Driven Hypertranscription and Controls Neural Progenitor Number [RNA-seq]

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The Hippo Pathway Prevents YAP/TAZ–Driven Hypertranscription and Controls Neural Progenitor Number [ChIP-seq]

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The Hippo Pathway Prevents YAP/TAZ–Driven Hypertranscription and Controls Neural Progenitor Number

Project description:The Hippo Pathway Prevents YAP/TAZ–Driven Hypertranscription and Controls Neural Progenitor Number

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The Hippo Pathway Prevents YAP/TAZ–Driven Hypertranscription and Controls Neural Progenitor Number [microarray]

Project description:The Hippo Pathway Prevents YAP/TAZ–Driven Hypertranscription and Controls Neural Progenitor Number [microarray]

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The Hippo Pathway Prevents YAP/TAZ–Driven Hypertranscription and Controls Neural Progenitor Number [RNA-seq]

Project description:The Hippo Pathway Prevents YAP/TAZ–Driven Hypertranscription and Controls Neural Progenitor Number [RNA-seq]

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Regulation of gene expression by the Hippo effectors, Taz and Yap, in muscle stem cells

Project description:The Hippo pathway downstream effectors, Yap and Taz, play key roles in cell proliferation and tissue growth, regulating gene expression especially via interaction with Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analysed gene expression changes driven by Taz and compared these to Yap mediated changes to the transcriptome by measurement of gene expression on Affymetrix microarrays. To interrogate overlapping and unique transcriptional changes driven by these Hippo effectors, satellite cell-derived myoblasts were transduced with constitutively active TAZ S89A or YAP S127A retrovirus for 24h or 48h, with empty retrovirus as control. Triplicate microarray analyses of empty vector controls, hYAP1 S127A and TAZ S89A transgenic primary myoblasts were conducted.

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The Hippo Pathway Prevents YAP/TAZ-Driven Hypertranscription and Controls Neural Progenitor Number.

Project description:The Hippo pathway controls the activity of YAP/TAZ transcriptional coactivators through a kinase cascade. Despite the critical role of this pathway in tissue growth and tumorigenesis, it remains unclear how YAP/TAZ-mediated transcription drives proliferation. By analyzing the effects of inactivating LATS1/2 kinases, the direct upstream inhibitors of YAP/TAZ, on mouse brain development and applying cell-number-normalized transcriptome analyses, we discovered that YAP/TAZ activation causes a global increase in transcription activity, known as hypertranscription, and upregulates many genes associated with cell growth and proliferation. In contrast, conventional read-depth-normalized RNA-sequencing analysis failed to detect the scope of the transcriptome shift and missed most relevant gene ontologies. Following a transient increase in proliferation, however, hypertranscription in neural progenitors triggers replication stress, DNA damage, and p53 activation, resulting in massive apoptosis. Our findings reveal a significant impact of YAP/TAZ activation on global transcription activity and have important implications for understanding YAP/TAZ function.

| S-EPMC6296252 | biostudies-literature

Functional characterizations of the Hippo pathway effectors YAP and TAZ

Project description:The Hippo pathway plays an important role in regulating tissue homeostasis, and its effectors YAP and TAZ are responsible for mediating the vast majority of its physiological functions. Although YAP and TAZ are thought to be largely redundant and similarly regulated by Hippo signaling, they have developmental, structural, and physiological differences which suggest there may be differences in their regulation and downstream functions. To better understand the functions of YAP and TAZ in the Hippo pathway, we generated knockout cells and evaluated them in response to many conditions and stimuli. Here, we used RNA-seq to identify and compare differences in the transcriptional profiles between the YAP and TAZ.

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The effect of YAP/TAZ knockdown on the intestinal epithelium

Project description:The Hippo pathway plays a crucial in organ size control during development and tissue homeostasis in adult life. To examine a role for Hippo signaling in the intestinal epithelium, we analyzed gene expression patterns in the mouse intestinal epithelilum transfected with siRNAs or expression plasmids for shRNAs targeting the Hippo pathway effectors, YAP and TAZ. We performed two independent series of experiments (siGFP (n=3) vs siYAP/siTAZ (n=3), and shLacZ (n=1) vs shYAP/shTAZ (n=1)). Control siRNA (siGFP), YAP/TAZ siRNAs, or expression plasmids for control shRNA (shLacZ) or YAP/TAZ shRNAs were introduced into the mouse intestinal epithelium by the newly-developed in vivo transfection method. Four days after transfection, intestinal epithelial cells were isolated from the tissues and total RNA was extracted.

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