bims-ectoca 2024-04-21 papers

Issue of 2024‒04‒21
two papers selected by
Ankita Daiya, Birla Institute of Technology and Science

Epigenomics. 2024 Apr 19.

Current trends in clinical trials and the development of small molecule epigenetic inhibitors as cancer therapeutics.

Epigenetic mechanisms control and regulate normal chromatin structure and gene expression patterns, with epigenetic dysregulation observed in many different cancer types. Importantly, epigenetic modifications are reversible, offering the potential to silence oncogenes and reactivate tumor suppressors. Small molecule drugs manipulating these epigenetic mechanisms are at the leading edge of new therapeutic options for cancer treatment. The clinical use of histone deacetyltransferases inhibitors (HDACi) demonstrates the effectiveness of targeting epigenetic mechanisms for cancer treatment. Notably, the development of new classes of inhibitors, including lysine acetyltransferase inhibitors (KATi), are the future of epigenetic-based therapeutics. We outline the progress of current classes of small molecule epigenetic drugs for use against cancer (preclinical and clinical) and highlight the potential market growth in epigenetic-based therapeutics.

Keywords: HAT; KAT; acetyltransferase; cancer; epigenetic; inhibitor; lysine; precision; small molecule; targeted; therapeutic

DOI: https://doi.org/10.2217/epi-2023-0443

Curr Opin Genet Dev. 2024 Apr 17. pii: S0959-437X(24)00043-1. [Epub ahead of print]86 102194

Attraction and disruption: how loop extrusion and compartmentalisation shape the nuclear genome.

Mikhail Magnitov, Elzo de Wit.

Chromatin loops, which bring two distal loci of the same chromosome into close physical proximity, are the ubiquitous units of the three-dimensional genome. Recent advances in understanding the spatial organisation of chromatin suggest that several distinct mechanisms control chromatin interactions, such as loop extrusion by cohesin complexes, compartmentalisation by phase separation, direct protein-protein interactions and others. Here, we review different types of chromatin loops and highlight the factors and processes involved in their regulation. We discuss how loop extrusion and compartmentalisation shape chromatin interactions and how these two processes can either positively or negatively influence each other.

DOI: https://doi.org/10.1016/j.gde.2024.102194