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A new element in the gene expression puzzle

The addition of an acetyl group on lysine 122 affects its interaction with DNA and thus promotes the eviction of the histone. The space created allows arrival of transcription proteins and thus expression of the gene.

Regulation of Transcription through Acetylation of H3K122 on the Lateral Surface of the Histone Octamer.

Tropberger P, Pott S, Keller C, Kamieniarz-Gdula K, Caron M, Richter F, Li G, Mittler G, Liu ET, Bühler M, Margueron R, Schneider R.

Cell Feb. 14, 2013


Feb. 14, 2013

Discovering the mechanisms underlying gene expression is crucial to understand e.g. cell division, development or cancer formation. The team of Robert Schneider at the IGBMC has discovered a new mechanism that directly regulates the expression of genes. Their results are published on 14th of February in the journal Cell.

 

 

When comparing a neuron and a muscle cell, their appearance differs in many ways. Yet within the same organism, each cell has the same genetic heritage. These morphological differences can be explained by the fact that some genes are specifically expressed in one cell type and not in others. For many years, the scientific community has made efforts to understand the phenomena of “epigenetic modifications”, which are implicated in this cell type-specific regulation of gene expression without involving alterations in the DNA sequence. These modifications include the addition of small chemical groups on DNA or proteins involved in the packaging of DNA and can control the state of DNA condensation.


During a cell’s life, its DNA undergoes various states of condensation. For example, mitotic chromosomes are the manifestation of the highest state of chromatin compaction. Histones are proteins that shape the architecture of the genetic material of a cell by organizing the DNA. The DNA is wrapped around these histones, and they play a fundamental role in the level of DNA compaction. To date, the main sites of modifications known are located in the tails of the histone proteins. They undergo additions and removals of e.g. small acetyl or methyl groups, which can be indicative of the state of gene expression.


In partnership with researchers at the Institut Curie, Robert Schneider’s team at the IGBMC revealed that the addition of a single acetyl group in the central globular domain of a histone has a direct effect on gene expression. This addition of an acetyl group to a particular amino acid, lysine 122 of histone type H3, decreases the interaction between histones and DNA. This acetylation stimulates gene expression by promoting the expulsion of histones. Thus, this portion of DNA becomes accessible for binding by the proteins responsible for transcription, resulting in higher gene expression.


This work demonstrated for the first time a direct functional link between a histone modification at a particular amino acid with transcriptional activity. It suggests a causative function for histone modifications, rather than being a by-product of transcription. The next step will be to delve deeper into the hidden and complex mechanisms that regulate this acetylation.

 

By revealing new insights into how “epigenetic modifications” function, this study significantly contributes to a better understanding of the regulation of gene expression, which has implications in healthy individuals as well as in pathological contexts such as cancer.

Imprimer Envoyer

Université de Strasbourg
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