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: UNIPROT:P15088 (
mast cell
)
14,925
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
DNA methylation and specifically the DNA methyltransferase enzyme DNMT3A are involved in the pathogenesis of a variety of hematological diseases and in regulating the function of immune cells. Although altered DNA methylation patterns and mutations in
DNMT3A
correlate with
mast cell
proliferative disorders in humans, the role of DNA methylation in
mast cell
biology is not understood. By using mast cells lacking
Dnmt3a
, we found that this enzyme is involved in restraining
mast cell
responses to acute and chronic stimuli, both in vitro and in vivo. The exacerbated
mast cell
responses observed in the absence of
Dnmt3a
were recapitulated or enhanced by treatment with the demethylating agent 5-aza-2'-deoxycytidine as well as by down-modulation of
Dnmt1
expression, further supporting the role of DNA methylation in regulating
mast cell
activation. Mechanistically, these effects were in part mediated by the dysregulated expression of the scaffold protein
IQGAP2
, which is characterized by the ability to regulate a wide variety of biological processes. Altogether, our data demonstrate that DNMT3A and DNA methylation are key modulators of
mast cell
responsiveness to acute and chronic stimulation.
...
PMID:
Dnmt3a
restrains mast cell inflammatory responses. 2816 89
