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Updated: May 21, 2026
09:11
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Multiple histone methyl and acetyltransferase complex components bind the HLA-DRA gene.
1Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Plos One
|June 16, 2012
Summary
Histone modifications regulate Major Histocompatibility Complex class II (MHC-II) gene expression, establishing a stable epigenetic state upon activation. Key transcription factors and protein complexes like MLL and GCN5 are crucial for this process.
Area of Science:
- Immunology
- Epigenetics
- Molecular Biology
Background:
- Major histocompatibility complex class II (MHC-II) genes are vital for adaptive immunity.
- Histone modifications and their regulators in MHC-II gene activation are not fully understood.
Purpose of the Study:
- To define the scope and distribution of histone modifications during MHC-II gene activation.
- To identify the protein complexes responsible for these modifications.
Main Methods:
- Studied histone modifications in interferon-γ induced epithelial cells, B cells, and MHC-II deficient B-cell mutants using the HLA-DRA gene as a model.
- Employed a dual crosslinking chromatin immunoprecipitation method to detect interacting histone modifying complexes.
Main Results:
- Active transcription of HLA-DRA involved reduced nucleosome density and distinct patterns of histone acetylation and methylation.
- Most modifications depended on RFX or CIITA binding, establishing a stable epigenetic state.
- Identified components of MLL methyltransferase and GCN5 acetyltransferase complexes, including ATAC and STAGA, with some MLL components being CIITA-independent.
Conclusions:
- MHC-II gene activation involves a dynamic network of histone modifications orchestrated by multiple protein complexes.
- These modifications create a stable epigenetic memory crucial for sustained immune response.
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