How to count the position of epigenomic modifications from the end

October 17, 2023

Discovery of drug target pockets for cancer control

A joint research group of RIKEN Center for Biosystems Dynamics Research, RIKEN Center for Integrative Medical Sciences, RIKEN CSRS, and Yokohama City University has discovered a mechanism by which GAS41, a protein is highly expressed in many types of cancer cells, recognizes acetylated modifications of histone H3 proteins, which are responsible for epigenetic information, and subsequently activates the expression of specific genes.

The genomic DNA of eukaryotic cells, including humans, is condensed into a structure called a nucleosome, and the epigenome controls which gene nucleosomes are unraveled prior to transcription.

In this study, the joint research group analyzed the structure and function of GAS41 using methods from structural biology, biochemistry, and cell biology. As a result, it was elucidated that the GAS41 protein recognizes the “N-terminus” and the “acetylation modification of the 14th or 27th lysine residue from the N-terminus” of histone H3 using different pockets, and promotes the introduction of a histone variant protein called H2A.Z into the nucleosome, thereby facilitating the transcription of specific genes.

The findings from this research are expected to lead to the rational development of regulatory molecules that suppress the proliferation of various types of cancer cells in which GAS41 is highly expressed.

Original article

Proceedings of the National Academy of Sciences of the United States of America
doi: 10.1073/pnas.2304103120

M. Kikuchi, S. Takase, T.i Konuma, K. Noritsugu, S. Sekine, T. Ikegami, A. Ito, T. Umehara,

"GAS41 promotes H2A.Z deposition through recognition of the N terminus of histone H3 by the YEATS domain".

Contact

Akihiro Ito
Senior Visiting Scientist
Chemical Genomics Research Group