Molecular Medicine

, Volume 23, Issue 1, pp 196–203 | Cite as

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

  • Ding-Sheng Jiang
  • Xin Yi
  • Rui Li
  • Yun-Shu Su
  • Jing Wang
  • Min-Lai Chen
  • Li-Gang Liu
  • Min Hu
  • Cai Cheng
  • Ping Zheng
  • Xue-Hai Zhu
  • Xiang Wei
Research Article


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.



This work was supported by grants from the National Natural Science Foundation of China (81370201, 81600188, 81370264), the National Key Scientific Instrument Special Program of China (2013YQ030923-0607), the Natural Science Foundation of Hubei Province (2016CFB162) and the Fundamental Research Funds for the Central Universities (2042016kf0074).


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Authors and Affiliations

  • Ding-Sheng Jiang
    • 1
    • 2
    • 3
  • Xin Yi
    • 4
    • 5
    • 6
  • Rui Li
    • 1
  • Yun-Shu Su
    • 1
  • Jing Wang
    • 1
  • Min-Lai Chen
    • 1
  • Li-Gang Liu
    • 1
  • Min Hu
    • 1
  • Cai Cheng
    • 1
  • Ping Zheng
    • 1
  • Xue-Hai Zhu
    • 1
    • 2
    • 3
  • Xiang Wei
    • 1
    • 2
    • 3
    • 7
  1. 1.Division of Cardiothoracic and Vascular SurgeryHuazhong University of Science and TechnologyWuhanChina
  2. 2.Key Laboratory of Organ Transplantation, Ministry of EducationHuazhong University of Science and TechnologyWuhanChina
  3. 3.Key Laboratory of Organ Transplantation, Ministry of Health, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  4. 4.Department of CardiologyRenmin Hospital of Wuhan UniversityWuhanChina
  5. 5.Cardiovascular Research InstituteWuhan UniversityWuhanChina
  6. 6.Hubei Key Laboratory of CardiologyWuhanChina
  7. 7.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 CollegeHuazhong University of Science and TechnologyWuhanChina

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