The Histone Methyltransferase Mixed Lineage Leukemia (MLL) 3 May Play a Potential Role in Clinical Dilated Cardiomyopathy

Molecular Medicine

Research Article

Xin Yi¹  Yun-Shu Su²  Cai Cheng²  Min-Lai Chen²  Rui Li²  Li-Gang Liu²  Ping Zheng²  Jing Wang²  Min Hu²  Ding-Sheng Jiang³  Xue-Hai Zhu³  Xiang Wei⁴ 

[1] Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China;Cardiovascular Research Institute, Wuhan University, Wuhan, China;Hubei Key Laboratory of Cardiology, Wuhan, China;Division of Cardiothoracic and Vascular Surgery, Huazhong University of Science and Technology, Wuhan, China;Division of Cardiothoracic and Vascular Surgery, Huazhong University of Science and Technology, Wuhan, China;Key Laboratory of Organ Transplantation, Ministry of Education, Huazhong University of Science and Technology, Wuhan, China;Key Laboratory of Organ Transplantation, Ministry of Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Division of Cardiothoracic and Vascular Surgery, Huazhong University of Science and Technology, Wuhan, China;Key Laboratory of Organ Transplantation, Ministry of Education, Huazhong University of Science and Technology, Wuhan, China;Key Laboratory of Organ Transplantation, Ministry of Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Division of Cardiothoracic and Vascular Surgery, Key Laboratory of Organ Transplantation, Ministry of Education, Key Laboratory of Organ Transplantation, Ministry of Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095, Jiefang Ave., 430030, Wuhan, China;

关键词: ;   

DOI  :  10.2119/molmed.2017.00012

 received in 2017-01-17, accepted in 2017-08-01,  发布年份 2017

来源: Springer

【 摘 要 】

Histone modifications play a critical role In the pathological processes of dilated cardiomyopathy (DCM), while the role and expression pattern of histone methyltransferases (HMTs), especially mixed lineage leukemia (MLL) families, in DCM are unclear. To this end, 12 normal and 15 DCM heart samples were included in the present study. A murine cardiac remodeling model was induced by transverse aortic constriction (TAC). Real-time polymerase chain reaction was performed to detect the expression levels of MLL families in the mouse and human left ventricles. The mRNA level of MLL3 was significantly increased in the mouse hearts treated with TAC surgery. Compared with normal hearts, higher mRNA and protein level of MLL3 was detected in the DCM hearts, and its expression level was closely associated with left ventricular end diastolic diameter and left ventricular ejection fraction. However, there was no obvious change in the expression levels of other MLL families (MLL, MLL2, MLL4, MLL5, SETD1A and SETD1B) between control and DCM hearts or remodeled mouse hearts. Furthermore, the dimethylated histone H3 lysine 4 (H3K4me2) but not H3K4me3 was significantly increased in the DCM hearts. The protein levels of Smad3, GATA4 and EGR1, which might be regulated by MLL3, were remarkably elevated in the DCM hearts. Our hitherto unrecognized findings indicate that MLL3 has a potential role in the pathological processes of DCM by regulating H3K4me2 and the expression of Smad3, GATA4 and EGR1.

【 授权许可】

CC BY-NC-ND   
© The Author(s) 2017