Histone acylations and chromatin dynamics: concepts, challenges, and links to metabolism.

In eukaryotic cells, DNA is tightly packed with the help of histone proteins into chromatin. Chromatin architecture can be modified by various post-translational modifications of histone proteins. For almost 60 years now, studies on histone lysine acetylation have unraveled the contribution of this acylation to an open chromatin state with increased DNA accessibility, permissive for gene expression.

Succinylation of H3K122 destabilizes nucleosomes and enhances transcription.

Histone post-translational modifications (PTMs) are key players in chromatin regulation. The identification of novel histone acylations raises important questions regarding their role in transcription. In this study, we characterize the role of an acylation on the lateral surface of the histone octamer, H3K122 succinylation (H3K122succ), in chromatin function and transcription.

Designer epigenome modifiers enable robust and sustained gene silencing in clinically relevant human cells.

Targeted modulation of gene expression represents a valuable approach to understand the mechanisms governing gene regulation. In a therapeutic context, it can be exploited to selectively modify the aberrant expression of a disease-causing gene or to provide the target cells with a new function. Here, we have established a novel platform for achieving precision epigenome editing using designer epigenome modifiers (DEMs).

Generation of TALE-Based Designer Epigenome Modifiers.

Manipulation of gene expression can be facilitated by editing the genome or the epigenome. Precise genome editing is traditionally achieved by using designer nucleases which are generally exploited to eliminate a specific gene product. Upon the introduction of a site-specific DNA double-strand break (DSB) by the nuclease, endogenous DSB repair mechanisms are in turn harnessed to induce DNA sequence changes that can result in target gene inactivation.

Loss of maternal Trim28 causes male-predominant early embryonic lethality.

Global DNA demethylation is a hallmark of embryonic epigenetic reprogramming. However, embryos engage noncanonical DNA methylation maintenance mechanisms to ensure inheritance of exceptional epigenetic germline features to the soma. Besides the paradigmatic genomic imprints, these exceptions remain ill-defined, and the mechanisms ensuring demethylation resistance in the light of global reprogramming remain poorly understood.