Human Disease Modeling Reveals Integrated Transcriptional and Epigenetic Mechanisms of NOTCH1 Haploinsufficiency

@article{Theodoris2015HumanDM,
  title={Human Disease Modeling Reveals Integrated Transcriptional and Epigenetic Mechanisms of NOTCH1 Haploinsufficiency},
  author={Christina V. Theodoris and Molong Li and Mark P. White and Lei Liu and Daniel He and Katherine S. Pollard and Benoit G Bruneau and Deepak Srivastava},
  journal={Cell},
  year={2015},
  volume={160},
  pages={1072-1086}
}
The mechanisms by which transcription factor haploinsufficiency alters the epigenetic and transcriptional landscape in human cells to cause disease are unknown. Here, we utilized human induced pluripotent stem cell (iPSC)-derived endothelial cells (ECs) to show that heterozygous nonsense mutations in NOTCH1 that cause aortic valve calcification disrupt the epigenetic architecture, resulting in derepression of latent pro-osteogenic and -inflammatory gene networks. Hemodynamic shear stress, which… CONTINUE READING
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References

Publications referenced by this paper.
Showing 1-10 of 42 references

Bone morphogenetic proteins: a critical review.

Cellular signalling • 2011
View 8 Excerpts
Highly Influenced

CD105 inhibits transforming growth factor-beta-Smad3 signalling.

Anticancer research • 2004
View 7 Excerpts
Highly Influenced

American Heart Association Statistics Committee and Stroke Statistics Subcommittee

A. S. Go, D. Mozaffarian, +7 authors S Franco
Circulation 129, • 2014
View 1 Excerpt

Long-range enhancer activity determines Myc sensitivity to Notch inhibitors in T cell leukemia.

Proceedings of the National Academy of Sciences of the United States of America • 2014

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