CityUHK research reveals modulating chromatin dynamics of H2B mutations, shedding lights on novel targeted therapy of breast cancer - EurekAlert!

AcknowledgementsWe thank Rie Shimano, Yukari Azuma, Eriko Tanaka, Mizuki Shinoda, Akie Takahashi, Hiroko Egashira, and Taeko Kawakami for technical support for molecular genetics and Ayami Furuta for technical support for RNA-seq. Seeds for SALK lines and auxin-related reporters were obtained from ABRC. FundingThis work was supported by a JSPS KAKENHI Grant-in-Aid for JSPS Fellows (24KJ1694) to Y. F.; a JSPS KAKENHI Grant-in-Aid for Transformative Research Areas (A) (25H01834) to T. K.; the Cross-ministerial Strategic Innovation Promotion Program (SIP), “Technologies for Smart Bio-industry and Agriculture,” funded by the Cabinet Office, Government of Japan, to Y. I.; a JSPS KAKENHI Grant-in-Aid for Scientific Research (C) (23K05809) to T. S.; the U. S. National Science Foundation (IOS-2319036) to D. W.; a JSPS KAKENHI Grant-in-Aid for Transformative Research Areas (A) (22H05176) and a Grant-in-Aid for Scientific Research (A) (26H02380) to T.

We’re sharing this article early to provide faster access to peer-reviewed, accepted research. It is citable and carries a permanent DOI. This version is subject to further edits and will be replaced automatically by the final Version of Record. All legal disclaimers apply. AbstractFOXO transcription factors are critical for cellular homeostasis and the stress response and have been implicated in longevity in several species. Yet, how these factors function at the chromatin level in differing conditions in human cells is poorly understood. Here, we take an integrated multi-omics approach to identify the chromatin-level mechanisms by which FOXO3 coordinates transcriptional programs in replicating cells and in a model of cellular senescence. In a DNA-damage induced senescence, FOXO3 levels are elevated early in senescence entry. Increased FOXO3 expression induces expression of chromatin remodeling factors, and impacts chromatin accessibility across the genome together with SWI/SNF chromatin remodelers.