Long non-coding RNA LHX1-DT regulates cardiomyocyte differentiation through H2A.Z-mediated LHX1 transcriptional activation

被引：6

作者：

Yu, Qi ^{[1
,2
]}

Cai, Benzhi ^{[1
,3
,4
]}

Zhang, Yong ^{[1
]}

Xu, Juan ^{[5
]}

Liu, Dongping ^{[1
]}

Zhang, Xiyang ^{[1
]}

Han, Zhenbo ^{[6
]}

Ma, Yingying ^{[5
]}

Jiao, Lei ^{[1
]}

Gong, Manyu ^{[1
]}

Yang, Xuewen ^{[1
]}

Wang, Yanying ^{[1
]}

Li, Haodong ^{[1
]}

Sun, Lihua ^{[1
]}

Bian, Yu ^{[1
]}

Yang, Fan ^{[1
]}

Xuan, Lina ^{[1
]}

Wu, Haodi ^{[2
]}

Yang, Baofeng ^{[1
,7
]}

Zhang, Ying ^{[1
]}

机构：

[1] Harbin Med Univ, State Prov Key Labs Biomed Pharmaceut China, Key Lab Cardiovasc Med Res, Dept Pharmacol,Minist Educ,Coll Pharm, Harbin 150081, Heilongjiang, Peoples R China

[2] Univ Pittsburgh, Blood Vasc Med Inst, Dept Med, Div Cardiol,Sch Med, Pittsburgh, PA 15261 USA

[3] Harbin Med Univ, Dept Pharm, Affiliated Hosp 2, Harbin 150081, Peoples R China

[4] Harbin Med Univ, Dept Pharmacol, Key Lab Cardiovasc Med Res, Minist Educ,Coll Pharm, Harbin 150081, Peoples R China

[5] Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin 150081, Heilongjiang, Peoples R China

[6] Univ Illinois, Coll Med, Dept Pharmacol & Regenerat Med, 909 S Wolcott Ave,COMRB 4100, Chicago, IL 60612 USA

[7] Chinese Acad Med Sci 2019RU070, Res Unit Noninfect Chron Dis Frigid Zone, Harbin 150086, Peoples R China

来源：

ISCIENCE | 2023年 / 26卷 / 11期

基金：

中国国家自然科学基金;

关键词：

CELL; H2A.Z; LNCRNA; EXPRESSION; FEATURES; GENES; OTX2;

D O I：

10.1016/j.isci.2023.108051

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Long non-coding RNAs (lncRNAs) play widespread roles in various processes. However, there is still limited understanding of the precise mechanisms through which they regulate early stage cardiomyocyte differentiation. In this study, we identified a specific lncRNA called LHX1-DT, which is transcribed from a bidirectional promoter of LIM Homeobox 1 (LHX1) gene. Our findings demonstrated that LHX1-DT is nu-clear-localized and transiently elevated expression along with LHX1 during early differentiation of cardi-omyocytes. The phenotype was rescued by overexpression of LHX1 into the LHX1-DT-/- hESCs, indi-cating LHX1 is the downstream of LHX1-DT. Mechanistically, we discovered that LHX1-DT physically interacted with RNA/histone-binding protein PHF6 during mesoderm commitment and efficiently re-placed conventional histone H2A with a histone variant H2A.Z at the promoter region of LHX1. In sum-mary, our work uncovers a novel lncRNA, LHX1-DT, which plays a vital role in mediating the exchange of histone variants H2A.Z and H2A at the promoter region of LHX1.

引用

页数：19

共 56 条

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