Histone variants and their post-translational modifications in primary human fat cells
Asa Jufvas1, Peter Strålfors, Alexander V Vener
1Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Plos One
|January 21, 2011
Summary
Researchers identified novel histone variants and modifications in human fat cells, enabling personalized epigenetic analysis for diseases like obesity and diabetes. This method allows for tailored medical treatments based on individual epigenetic profiles.
Area of Science:
- Human epigenetics
- Molecular biology
- Proteomics
Background:
- Human disease epigenetics requires direct study of human cells.
- Current methods are insufficient for comprehensive analysis of human histone variants and modifications.
Purpose of the Study:
- To develop a method for isolating and analyzing histones and their modifications from human adipocytes.
- To identify novel histone variants and modifications in human fat tissue.
- To explore the potential for personalized epigenetic analysis in relation to metabolic diseases.
Main Methods:
- Isolation of human adipocytes from subcutaneous abdominal fat tissue.
- Direct acid extraction of histones from whole adipocytes.
- Differential proteolysis and nanoLC/MS/MS with CID/ETD sequencing for peptide analysis.
- Identification of histone variants and post-translational modifications.
Main Results:
- Efficient histone extraction from adipocytes yielding 19 histone variants, including novel ones like HIST2H4B.
- Identification of 68 new histone modifications out of 78 total, with high inter-individual variability.
- Discovery of histone variants potentially involved in chromatin organization and X chromosome inactivation.
- Found histone variants previously described only as oocyte or testis specific.
Conclusions:
- Direct acid extraction of adipocytes provides a viable method for personal epigenetic analysis.
- This approach facilitates profiling of histone modifications linked to obesity, diabetes, and metabolic syndrome.
- Enables selection of individualized medical treatments based on patient-specific epigenetic data.
Related Concept Videos
02:32Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:32Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:30Histone Variants at the Centromere
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3 variants are also...
02:25Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
01:32Chromatin Modification in iPS Cells
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (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...
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...
01:12The Nucleosome Core Particle
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...