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New type of epigenetic mark identified in the human cell nucleus.

Epigenetics is a research field where DNA methylation or histone acetylation, as opposed to the DNA sequence, are studied as a tool for conveying traits to the next generation. Previously, epigenetics has been shown to be involved in pathogenesis or disease progression, proving to be a crucial area of research.  Now, a study from researchers led by Osaka University identifies the presence of a previously unknown protein modification that is a unique mark in human cell nucleus. The team state that their findings suggest the protein modification, known as Histone H4 lysine 20 acetylation (H4K20ac), is associated with gene repression, and the direct proof of H4K20ac in mammalian cells may uncover further mechanisms in disease progression.  The opensource study is published in the journal Scientific Reports.

Previous studies show that epigenetic factors, factors outside of the genetic sequence, are deeply involved in the development of various diseases. A histone, which is a component of chromatin consisting of DNA, receives post-translational modification for changing the function of protein as an epigenetic factor.  Histone modifications, such as lysine acetylation and methylation, play important roles in the epigenetic regulation of gene expression through chromatin structure changes.  The protein modification, H4K20ac, was only discovered in plant cells and its existence in mammalian cells has been indirectly proven.  The current study shows that H4K20ac is a unique acetylation mark associated with gene repression in the mammalian cell.

The current study investigates the function of H4K20ac using a specific monoclonal antibody and performing ChIP-seq analysis using HeLa-S3 cells. Results show that H4K20ac was enriched around the transcription start sites of minimally expressed genes.  Data findings show that the distribution of H4K20ac showed little correlation with known histone modifications, including histone H3 methylations.

Results show that H4K20ac was enriched around transcription start sites of minimally expressed and silent genes, and also in the gene body of expressed genes. The lab state that their findings suggest H4K20ac is a previously undescribed type of histone acetylation that is associated with gene repression.

The team surmise that their discovery of a new kind of histone acetylation modification will widen the field of  epigenetics, and by using H4K20ac, the scope of knowledge in pathogenesis or disease progression will be greatly raised in future studies.  For the future, the researchers state that they expect the development of numerous diseases such as metabolic disorders and cardiovascular diseases, as well as, cancer to be elucidated using H4K20ac, a new type of histone modification identified in this study.

Source: Osaka University


It was accepted that histone acetylation modifications are implicated only in gene activation "switch on".  Credit: Osaka University.
It was accepted that histone acetylation modifications are implicated only in gene activation “switch on”. Credit: Osaka University.



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