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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Decoding YAP dependent transcription in the liver.

Francesca Biagioni1, Ottavio Croci1, Silvia Sberna1

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The transcriptional coactivator YAP acts as a master regulator of liver cell growth. YAP reshapes the liver

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Area of Science:

  • Molecular Biology
  • Genomics
  • Cell Biology

Background:

  • The transcriptional coactivator YAP is a key regulator of cell growth.
  • YAP activity in the liver is associated with hepatomegaly, regeneration, dedifferentiation, and aggressive tumor growth.

Purpose of the Study:

  • To investigate the genomic mechanisms by which YAP induces significant biological changes in murine liver models.

Main Methods:

  • Genomic studies were conducted in murine models.
  • Analysis of YAP binding sites and transcriptional activity.
  • Investigation of YAP's effects on gene expression, cell proliferation, and tissue remodeling.

Main Results:

  • YAP binds the genome via TEAD, targeting both constitutive TEAD sites and pioneering embryonic enhancers.
  • YAP recruits BRD4 to activate transcription and represses HNF4a target genes.
  • YAP activation induces hepatocyte proliferation, tissue remodeling, immune cell modulation, and endothelial cell dedifferentiation.

Conclusions:

  • YAP is a master regulator of liver function, controlling genes involved in metabolism, proliferation, and inflammation.
  • YAP subverts lineage specification by antagonizing HNF4a and altering the liver's immune and vascular architecture.