G-quadruplexes sense natural porphyrin metabolites for regulation of gene transcription and chromatin landscapes

Genome Biology

Research

Pingping Fang¹  Conghui Li¹  Lingyu Lei¹  Tianyu Li¹  Jiaqin Ye¹  Honghong Wang¹  Fangteng Guo¹  Youquan Zhong¹  Ying Xiang¹  Ruijing Xiao¹  Yali Cui¹  Zhinang Yin¹  Beili Huang¹  Lingrui Wang¹  Yuchen Xia²  Kaiwei Liang³ 

[1] School of Basic Medical Sciences, Wuhan University, 430071, Wuhan, China;School of Basic Medical Sciences, Wuhan University, 430071, Wuhan, China;State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University, 430071, Wuhan, China;TaiKang Center for Life and Medical Sciences, TaiKang Medical School, Wuhan University, 430071, Wuhan, China;School of Basic Medical Sciences, Wuhan University, 430071, Wuhan, China;TaiKang Center for Life and Medical Sciences, TaiKang Medical School, Wuhan University, 430071, Wuhan, China;Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, 430071, Wuhan, China;

关键词: G-quadruplex;    Transcription initiation;    Hemin;    Porphyrins;    G4-CUT&Tag;    Chromatin landscapes;   

DOI  :  10.1186/s13059-022-02830-8

 received in 2022-06-20, accepted in 2022-12-02,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundG-quadruplexes (G4s) are unique noncanonical nucleic acid secondary structures, which have been proposed to physically interact with transcription factors and chromatin remodelers to regulate cell type-specific transcriptome and shape chromatin landscapes.ResultsBased on the direct interaction between G4 and natural porphyrins, we establish genome-wide approaches to profile where the iron-liganded porphyrin hemin can bind in the chromatin. Hemin promotes genome-wide G4 formation, impairs transcription initiation, and alters chromatin landscapes, including decreased H3K27ac and H3K4me3 modifications at promoters. Interestingly, G4 status is not involved in the canonical hemin-BACH1-NRF2-mediated enhancer activation process, highlighting an unprecedented G4-dependent mechanism for metabolic regulation of transcription. Furthermore, hemin treatment induces specific gene expression profiles in hepatocytes, underscoring the in vivo potential for metabolic control of gene transcription by porphyrins.ConclusionsThese studies demonstrate that G4 functions as a sensor for natural porphyrin metabolites in cells, revealing a G4-dependent mechanism for metabolic regulation of gene transcription and chromatin landscapes, which will deepen our knowledge of G4 biology and the contribution of cellular metabolites to gene regulation.

【 授权许可】

CC BY   
© The Author(s) 2022

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