Epigenetic Regulation of Endothelial Lineage Committed Genes in Pro-Angiogenic Hematopoietic and Endothelial Progenitor Cells

@article{Ohtani2011EpigeneticRO,
  title={Epigenetic Regulation of Endothelial Lineage Committed Genes in Pro-Angiogenic Hematopoietic and Endothelial Progenitor Cells},
  author={Kisho Ohtani and Georgios J. Vlachojannis and Masamichi Koyanagi and Jes-Niels Boeckel and Carmen Urbich and Ruxandra Farcas and Halvard Bonig and Victor E. Marquez and Andreas M. Zeiher and Stefanie Dimmeler},
  journal={Circulation Research},
  year={2011},
  volume={109},
  pages={1219–1229}
}
Rationale: Proangiogenic hematopoietic and endothelial progenitor cells (EPCs) contribute to postnatal neovascularization, but the mechanisms regulating differentiation to the endothelial lineage are unclear. Objective: To elucidate the epigenetic control of endothelial gene expression in proangiogenic cells and EPCs. Methods and Results: Here we demonstrate that the endothelial nitric oxide synthase (eNOS) promoter is epigenetically silenced in proangiogenic cells (early EPCs), CD34+ cells… 
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39 References

Histone deacetylase activity is essential for the expression of HoxA9 and for endothelial commitment of progenitor cells

HoxA9 is regulated by HDACs and is critical for postnatal neovascularization and acts as a master switch to regulate the expression of prototypical endothelial-committed genes and mediates the shear stress–induced maturation of endothelial cells.

The Expression of Endothelial Nitric-oxide Synthase Is Controlled by a Cell-specific Histone Code*

Findings provide strong evidence that the endothelial cell-specific expression of eNOS is controlled by cell- specific histone modifications.

Hypoxic Repression of Endothelial Nitric-oxide Synthase Transcription Is Coupled with Eviction of Promoter Histones*♦

Evidence is presented that hypoxia causes a rapid decrease in the transcription of the eNOS/NOS3 gene, accompanied by decreased acetylation and lysine 4 (histone H3) methylation of eNos proximal promoter histones, and that histone eviction rapidly resets histone marks and is a proximal event in the hypoxic repression of e NOS.

The Cell-specific Expression of Endothelial Nitric-oxide Synthase

This report is the first to show that promoter DNA methylation plays an important role in the cell-specific expression of a constitutively expressed gene in the vascular endothelium and addressed the functional consequences of methylation on eNOS transcription using transient transfection of in vitro methylated promoter/reporter constructs.

Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors.

Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells

It is indicated that eNOS expressed by bone marrow stromal cells influences recruitment of stem and progenitor cells, which may contribute to impaired regeneration processes in ischemic heart disease patients, who are characterized by a reduced systemic NO bioactivity.

Sox2 Transduction Enhances Cardiovascular Repair Capacity of Blood-Derived Mesoangioblasts

It is shown that clonally expandable, telomerase expressing progenitor cells can be isolated from peripheral blood of children and pluripotency of Sox-MABs was shown by demonstrating the generation of endodermal and ectodermal progenies.

Characterization of the Human Endothelial Nitric-oxide Synthase Promoter*

A detailed dissection of the functionally important cis-DNA elements and the multiprotein complexes implicated in the cooperative control of constitutive expression of the human eNOS gene in vascular endothelium revealed a surprising degree of cooperativity and complexity.

Cathepsin L is required for endothelial progenitor cell–induced neovascularization

It is concluded that CathL has a critical role in the integration of circulating EPC into ischemic tissue and is required for EPC-mediated neovascularization.

Identification of Hypoxia-response Element in the Human Endothelial Nitric-oxide Synthase Gene Promoter*

HeNOS is a hypoxia-inducible gene, whose transcription is stimulated through HIF-2 interaction with two contiguous HRE sites located at –5375 to –5366 of the heNOS promoter.