高迁移率族蛋白A1介导人类一氧化氮合酶2基因的表达。
High mobility group A1 protein mediates human nitric oxide synthase 2 gene expression.
作者信息
Takamiya Rina, Baron Rebecca M, Yet Shaw-Fang, Layne Matthew D, Perrella Mark A
机构信息
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
出版信息
FEBS Lett. 2008 Mar 5;582(5):810-4. doi: 10.1016/j.febslet.2008.02.008. Epub 2008 Feb 13.
Abstract
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.
摘要
一氧化氮合酶（NOS）2是一种在炎症期间产生NO的诱导型酶，其表达受转录调控。我们的目标是确定高迁移率族（HMG）A1是否参与人（h）NOS2基因的调控。使用一种HMGA1与DNA结合的小分子抑制剂，或一种显性负性形式的HMGA1，我们减弱了促炎刺激对hNOS2的诱导作用。HMGA1在hNOS2启动子-3506至-3375区域（一个以前未知参与hNOS2调控的区域）的结合，与上游增强子区域共同作用，促进了hNOS2启动子的诱导。我们证明了HMGA1在hNOS2调控中具有以前未知的作用。
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