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鉴定 HZF1 为 MEF2 转录因子的一个新的靶基因。

Identification of HZF1 as a novel target gene of the MEF2 transcription factor.

机构信息

Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, PR China.

出版信息

Mol Med Rep. 2011 May-Jun;4(3):465-9. doi: 10.3892/mmr.2011.465. Epub 2011 Mar 22.

Abstract

The MADS box-containing transcription factors MEF2A-D regulate the expression of most skeletal and cardiac muscle structural genes. Recently, a zinc finger protein called HZF1 was identified as a transcription factor, and found to be highly expressed in cardiac muscle. By screening the transcription regulatory region of HZF1, we found that myocyte enhancer factor 2 (MEF2) potentially recognizes and binds the regulatory region of the HZF1 gene. We also found that the knockdown of MEF2A endogenous expression in human aortic smooth muscle cells decreases the expression of HZF1, while the enforced expression of MEF2A in turn promotes the expression of HZF1. Furthermore, we employed the luciferase reporter system and chromatin immunoprecipitation (ChIP) to demonstrate that MEF2A does in fact bind the regulatory region of HZF1, which suggests that HZF1 is the direct target of MEF2A. Based on the fact that MEF2 proteins function as essential regulators of cardiac development and as important pathological factors for certain cardiac diseases, our finding that MEF2 positively regulates the expression of HZF1 may contribute to further research investigating the role of the zinc finger protein HZF1 in cardiac development and disease.

摘要

MADS 框转录因子 MEF2A-D 调节大多数骨骼肌和心肌结构基因的表达。最近,一种称为 HZF1 的锌指蛋白被鉴定为一种转录因子,并且在心肌中高度表达。通过筛选 HZF1 的转录调控区,我们发现肌细胞增强因子 2(MEF2)可能识别并结合 HZF1 基因的调控区。我们还发现,人主动脉平滑肌细胞中 MEF2A 内源性表达的敲低会降低 HZF1 的表达,而 MEF2A 的强制表达则反过来促进 HZF1 的表达。此外,我们采用了荧光素酶报告系统和染色质免疫沉淀(ChIP)来证明 MEF2A 确实结合 HZF1 的调控区,这表明 HZF1 是 MEF2A 的直接靶标。鉴于 MEF2 蛋白作为心脏发育的重要调节因子以及某些心脏疾病的重要病理因素,我们发现 MEF2 正向调节 HZF1 的表达,这可能有助于进一步研究锌指蛋白 HZF1 在心脏发育和疾病中的作用。

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