Epigenetic regulation of melanogenesis

Shihang Zhou; Hongliang Zeng; Jinhua Huang; Li Lei; Xiaoliang Tong; Si Li; Ying Zhou; Haoran Guo; Manal Khan; Liping Luo; Rong Xiao; Jing Chen; Qinghai Zeng

doi:10.1016/j.arr.2021.101349

Epigenetic regulation of melanogenesis

Ageing Res Rev. 2021 Aug:69:101349. doi: 10.1016/j.arr.2021.101349. Epub 2021 May 10.

Authors

Shihang Zhou¹, Hongliang Zeng², Jinhua Huang¹, Li Lei¹, Xiaoliang Tong¹, Si Li¹, Ying Zhou¹, Haoran Guo¹, Manal Khan¹, Liping Luo¹, Rong Xiao³, Jing Chen⁴, Qinghai Zeng⁵

Affiliations

¹ Department of Dermatology, Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, Hunan, 410013, PR China.
² Institute of Chinese Materia Medica, Hunan Academy of Chinese Medicine, Changsha, Hunan, 410013, PR China.
³ Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenetics, 139 Renmin Middle Road, Changsha, 410011, Hunan, PR China.
⁴ Department of Dermatology, Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, Hunan, 410013, PR China. Electronic address: 43700351@qq.com.
⁵ Department of Dermatology, Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, Hunan, 410013, PR China. Electronic address: zengqinghai@csu.edu.cn.

PMID: 33984527
DOI: 10.1016/j.arr.2021.101349

Abstract

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 melanogenesis-related 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.

Keywords: Chromatin remodelers; DNA methylation; Epigenetics; Histone modification; Melanogenesis; Noncoding RNAs.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Epigenesis, Genetic*
Gene Expression Regulation
Humans
Melanins* / metabolism
Melanocytes* / metabolism

Substances

Melanins