The TIP60 multiprotein complex is a sort of cellular “control unit” that regulates chromatin remodelling. Chromatin is the substance that makes up the nucleus of cells and consists of DNA wrapped around proteins like a ball of yarn. TIP60 plays a crucial role in the proper functioning of cells, regulating, among other things, gene expression, and its alterations can contribute to the onset of human diseases, including cancer and neurological development disorders.

For years, the Epigenetics and Cell Division Laboratory at Sapienza University (Charles Darwin Department of Biology and Biotechnology), coordinated by Patrizio Dimitri, has been studying the “non-canonical” functions performed by TIP60. “In particular”, says Dimitri, “we were intrigued by the observation that proteins known to perform chromatin functions moved from the nucleus to the sites of the mitotic apparatus that controls various stages of cell division”.

These observations, conducted on various organisms ranging from humans to Drosophila melanogaster (the fruit fly) and even plants, indicate that this phenomenon has been preserved throughout evolution. This need gave rise to the recent review, with the aim of taking stock of current knowledge and stimulating new directions of research in a field that is as promising as it is still largely unexplored.

The article, published in the journal Epigenetics & Chromatin, focuses in particular on what Dimitri called the mitotic journey of remodelling proteins, a phenomenon that reveals the moonlighting functions of the TIP60 complex, capable of performing different tasks in distinct cellular compartments, demonstrating surprising versatility.

This is a phenomenon of great interest because it suggests the existence of genetic-molecular mechanisms that are yet to be clarified and that play a fundamental role in controlling cell division and genome stability. Further investigation of these mechanisms could open up new perspectives in understanding diseases linked to defects in the processes of division and gene regulation. It is no coincidence that TIP60 represents a potential target for the development of future therapeutic strategies.

“The study also addresses key aspects of biological evolution”, notes Patrizio Dimitri. “Contrary to what one might think, evolution does not necessarily create entirely new genes or proteins. Much more often, it reuses and modifies existing molecules, adapting them to new tasks without causing them to lose their original functions entirely”.

The research was conducted thanks to funding obtained from the Ministry of University and Research (PRIN 2022 Project: Integrating genetic models to mechanistically dissect cytokinesis failure in neurodevelopmental disorders).

References:

The multitalented TIP60 chromatin remodeling complex: wearing many hats in epigenetic regulation, cell division and diseases - Maria Virginia Santopietro, Diego Ferreri, Yuri Prozzillo, Patrizio Dimitri & Giovanni Messina - https://epigeneticsandchromatin.biomedcentral.com