Apr 5, 2020

ERG orchestrates chromatin interactions to drive prostate cell fate reprogramming

BioRxiv : the Preprint Server for Biology
F. LiD. Gao

Abstract

While cancer is commonly perceived as a disease of dedifferentiation, the hallmark of early stage prostate cancer is paradoxically the loss of more plastic basal cells and the abnormal proliferation of more differentiated secretory luminal cells. However, the mechanism of prostate cancer pro-luminal differentiation is largely unknown. Through integrating analysis of the transcription factors (TFs) from 806 human prostate cancers, we have identified that ERG highly correlated with prostate cancer luminal subtyping. ERG overexpression in luminal epithelial cells inhibits its normal plasticity to transdifferentiate into basal lineage and ERG supersedes PTEN-loss which favors basal differentiation. ERG knock-out disrupted prostate cell luminal differentiation, whereas AR knock-out had no such effects. Trp63 is a known master regulator of prostate basal lineage. Through analysis of 3D chromatin architecture, we found that ERG binds and inhibits the enhancer activity and chromatin looping of a Trp63 distal enhancer, thereby silencing its gene expression. Specific deletion of the distal ERG binding site resulted in the loss of ERG-mediated inhibition of basal differentiation. Thus, ERG orchestrates chromatin interactions and regulates...Continue Reading

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

Eukaryotic Initiation Factor-4G
Norovirus (antigen)
Carboxy-Terminal Amino Acid
Genome
Norovirus
Amino Acids, I.V. solution additive
Complex (molecular entity)
Murine
Eukaryotic Initiation Factor-4A
Protein Biosynthesis

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Olga KlezovitchValeri Vasioukhin
Neoplasia : an International Journal for Oncology Research
Kyung ParkMark A Rubin
Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
Geert J L H van LeendersJan Trapman
Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
Kathryn L PenneyLorelei A Mucci
© 2020 Meta ULC. All rights reserved