Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0016719 (
Friedreich's ataxia
)
2,098
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The
CCCTC-binding factor
(
CTCF
) is a versatile transcriptional regulator required for embryogenesis, but its function in vascular development or in diseases with a vascular component is poorly understood. Here, we found that endothelial Ctcf is essential for mouse vascular development and limits accumulation of reactive oxygen species (ROS). Conditional knockout of
Ctcf
in endothelial progenitors and their descendants affected embryonic growth, and caused lethality at embryonic day 10.5 because of defective yolk sac and placental vascular development. Analysis of global gene expression revealed
Frataxin
(
Fxn
), the gene mutated in
Friedreich's ataxia
(
FRDA
), as the most strongly down-regulated gene in Ctcf-deficient placental endothelial cells. Moreover,
in vitro
reporter assays showed that Ctcf activates the
Fxn
promoter in endothelial cells. ROS are known to accumulate in the endothelium of
FRDA
patients. Importantly, Ctcf deficiency induced ROS-mediated DNA damage in endothelial cells
in vitro
, and in placental endothelium
in vivo
Taken together, our findings indicate that Ctcf promotes vascular development and limits oxidative stress in endothelial cells. These results reveal a function for Ctcf in vascular development, and suggest a potential mechanism for endothelial dysfunction in
FRDA
.
...
PMID:The transcriptional regulator CCCTC-binding factor limits oxidative stress in endothelial cells. 2961 Feb 76
