Regulation of Melanophilin (Mlph) gene expression by the glucocorticoid receptor (GR)

Sci Rep. 2021 Aug 19;11(1):16813. doi: 10.1038/s41598-021-96276-w.

Abstract

Mlph plays a crucial role in regulating skin pigmentation through the melanosome transport process. Although Mlph is a major component involved in melanosome transport, the mechanism that regulates the expression of the Mlph gene has not been identified. In this study, we demonstrate that Mlph expression is regulated by the glucocorticoid receptor (GR). Alteration of GR activity using a specific GR agonist or antagonist only regulated the expression of Mlph among the 3 key melanosome transport proteins. Translocation of GR from the cytosol into the nucleus following Dex treatment was confirmed by separating the cytosol and nuclear fractions and by immunofluorescence staining. In ChIP assays, Dex induced GR binding to the Mlph promoter and we determined that Dex induced the GR binding motif on the Mlph promoter. Our findings contribute to understanding the regulation of Mlph expression and to the novel role of GR in Mlph gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Base Sequence
  • Biological Transport / drug effects
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Dexamethasone / pharmacology
  • Gene Expression Regulation* / drug effects
  • Hydrocortisone / blood
  • Melanosomes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Promoter Regions, Genetic / genetics
  • Protein Binding / drug effects
  • Receptors, Glucocorticoid / agonists
  • Receptors, Glucocorticoid / metabolism*
  • Up-Regulation / drug effects

Substances

  • Adaptor Proteins, Signal Transducing
  • Mlph protein, mouse
  • Receptors, Glucocorticoid
  • Dexamethasone
  • Hydrocortisone