Epigenetic regulation of melanogenesis

被引：97

作者：

Zhou, Shihang ^{[1
]}

Zeng, Hongliang ^{[2
]}

Huang, Jinhua ^{[1
]}

Lei, Li ^{[1
]}

Tong, Xiaoliang ^{[1
]}

Li, Si ^{[1
]}

Zhou, Ying ^{[1
]}

Guo, Haoran ^{[1
]}

Khan, Manal ^{[1
]}

Luo, Liping ^{[1
]}

Xiao, Rong ^{[3
]}

Chen, Jing ^{[1
]}

Zeng, Qinghai ^{[1
]}

机构：

[1] Cent South Univ, Xiangya Hosp 4, Dept Dermatol, Changsha 410013, Hunan, Peoples R China

[2] Hunan Acad Chinese Med, Inst Chinese Mat Med, Changsha 410013, Hunan, Peoples R China

[3] Cent South Univ, Hunan Key Lab Med Epigenet, Second Xiangya Hosp, Dept Dermatol, 139 Renmin Middle Rd, Changsha 410011, Hunan, Peoples R China

来源：

AGEING RESEARCH REVIEWS | 2021年 / 69卷

基金：

中国国家自然科学基金;

关键词：

Epigenetics; DNA methylation; Histone modification; Chromatin remodelers; Noncoding RNAs; Melanogenesis; ACTIVE DNA DEMETHYLATION; TRANSCRIPTION FACTOR; MELANIN SYNTHESIS; INHIBITS MELANOGENESIS; STIMULATED MELANOGENESIS; CELL-PROLIFERATION; DOWN-REGULATION; NONCODING RNAS; MELANOCYTE; EXPRESSION;

D O I：

10.1016/j.arr.2021.101349

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Melanogenesis is a complex process in which melanin is synthesized in melanocytes and transported to keratinocytes, which involves multiple genes and signaling pathways. Epigenetics refers to the potential genetic changes that affect gene expression without involving changes in the original sequence of DNA nucleotides. DNA methylation regulates the expression of key genes such as tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), dopachrome tautomerase (DCT) and microphthalmia-associated transcription factor (MITF), as well as paracrine factors such as stem cell factor (SCF) and endothelin-1 (ET-1) in melanogenesis. Potential DNA methylation sites are present in the genes of melanogenesis-related signaling pathways such as "Wnt", "PI3K/Akt/CREB" and "MAPK". H3K27 acetylation is abundant in melanogenesis-related genes. Both the upstream activation and downstream regulation of MITF depend on histone acetyltransferase CBP/p300, and pH-induced H3K27 acetylation may be the amplifying mechanism of MITF's effect. HDAC1 and HDAC10 catalyze histone deacetylation of melanogenesis-related gene promoters. Chromatin remodelers SWI/SNF complex and ISWI complex use the energy of ATP hydrolysis to rearrange nucleosomes, while their active subunits BRG1, BRM and BPTF, act as activators and cofactors of MITF. MicroRNAs (miRNAs) can directly target a large number of melanogenesisrelated genes, while long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) regulate melanogenesis in a variety of ways. Interactions exist among the epigenetic mechanisms of melanogenesis. For example, the methyl CpG binding domain protein 2 (MeCP2) links DNA methylation, histone deacetylation, and histone methylation. Epigenetic-based therapy provides novel opportunities for treating dermatoses that are caused by pigmentation disturbances. This review summarizes the epigenetic regulation mechanisms of melanogenesis, and examines the pathogenesis and treatment of epigenetics in pigmentation disorders.

引用

页数：14

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