High mobility group A1 protein mediates human nitric oxide synthase 2 gene expression.
Nitric oxide synthase (NOS)2, an inducible enzyme that produces NO during inflammation, is transcriptionally regulated. Our goal was to determine whether high mobility group (HMG)A1 contributes to human (h)NOS2 gene regulation. Using a small molecule inhibitor of HMGA1 binding to DNA, or a dominant-negative form of HMGA1, we blunted the induction of hNOS2 by pro-inflammatory stimuli. Binding of HMGA1 in the region -3506 to -3375 of the hNOS2 promoter, a region not previously known to be involved in hNOS2 regulation, contributed to the induction of hNOS2 promoter in conjunction with upstream enhancer regions. We demonstrate a previously unknown role for HMGA1 in the regulation of hNOS2.
Takamiya
Rina
R
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Baron
Rebecca M
RM
Yet
Shaw-Fang
SF
Layne
Matthew D
MD
Perrella
Mark A
MA
D001483:Base Sequence; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D004214:Distamycins / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005799:Genes, Dominant; D025741:HMGA1a Protein / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion
D016207:Cytokines; D004214:Distamycins; D012333:RNA, Messenger; D025741:HMGA1a Protein; C030000:stallimycin; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II