Related Experiment Video
Updated: Jun 1, 2025

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Acetylation-enhanced Sp1 transcriptional activity suppresses Mlph expression
Chan Song Jo1, Hairu Zhao1, Jae Sung Hwang2
1Department of Genetics and Biotechnology, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, Korea.
Abstract:
Melanosome transport is regulated by major proteins, including Rab27a, Melanophilin (Mlph), and Myosin Va (Myo-Va), that form a tripartite complex. Mutation of these proteins causes melanosome aggregation around the nucleus. Among these proteins, Mlph is a linker between Rab27a and Myo-Va. There are some studies about the regulation of Mlph transcriptional expression. However, its regulation by post-translational modifications remains unclear. In this study, inhibition of HDACs by SAHA and TSA disrupted melanosome transport, causing melanosome aggregation. Specifically, we identified a novel mechanism in which HDAC5 regulates Mlph expression via Sp1. Knockdown of HDAC5 increased the acetylation of Sp1 and the binding to the Mlph promoter, thereby modulating its expression. This study highlights the crucial role of HDAC5 in melanosome transport through its interaction with Sp1. These findings suggest that HDAC5-mediated deacetylation is pivotal in the post-translational modification of melanosome transport, providing insights into the molecular mechanisms underlying this process.
Insights
Histone deacetylase 5 (HDAC5) regulates melanosome transport by controlling Melanophilin (Mlph) expression. This study reveals HDAC5
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Melanosome transport relies on the tripartite complex of Rab27a, Melanophilin (Mlph), and Myosin Va (Myo-Va).
- Mutations in these proteins lead to melanosome aggregation near the nucleus.
- While Mlph transcriptional regulation is studied, its post-translational modification control is not well understood.
Purpose of the Study:
- To investigate the role of post-translational modifications in regulating Mlph expression.
- To elucidate the specific mechanism by which HDAC5 influences melanosome transport.
Main Methods:
- Inhibition of histone deacetylases (HDACs) using SAHA and TSA.
- Knockdown of HDAC5.
- Analysis of Sp1 acetylation and its binding to the Mlph promoter.
Main Results:
- HDAC inhibition disrupted melanosome transport, causing aggregation.
- HDAC5 was identified as a regulator of Mlph expression via Sp1.
- HDAC5 knockdown increased Sp1 acetylation and its binding to the Mlph promoter, altering Mlph expression.
Conclusions:
- HDAC5 plays a critical role in melanosome transport through its interaction with Sp1.
- HDAC5-mediated deacetylation is a key post-translational modification in melanosome transport regulation.
- This study provides novel insights into the molecular mechanisms governing melanosome transport.
Related Concept Videos
Histone Modification
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Abnormal Proliferation
Chromatin Modification in iPS Cells
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
RNA Polymerase II Accessory Proteins
Spreading of Chromatin Modifications
Writers
The writer...
Master Transcription Regulators

