Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Polyadenylation of Histone H3.1 mRNA Promotes Cell Transformation by Displacing H3.3 from Gene Regulatory Elements.

Authors: Chen, Danqi; Chen, Qiao Yi; Wang, Zhenjia; Zhu, Yusha; Kluz, Thomas; Tan, Wuwei; Li, Jinquan; Wu, Feng; Fang, Lei; Zhang, Xiaoru; He, Rongquan; Shen, Steven; Sun, Hong; Zang, Chongzhi; Jin, Chunyuan; Costa, Max

Published In iScience, (2020 Sep 01)

Abstract: Replication-dependent canonical histone messenger RNAs (mRNAs) do not terminate with a poly(A) tail at the 3' end. We previously demonstrated that exposure to arsenic, an environmental carcinogen, induces polyadenylation of canonical histone H3.1 mRNA, causing transformation of human cells in vitro. Here we report that polyadenylation of H3.1 mRNA increases H3.1 protein, resulting in displacement of histone variant H3.3 at active promoters, enhancers, and insulator regions, leading to transcriptional deregulation, G2/M cell-cycle arrest, chromosome aneuploidy, and aberrations. In support of these observations, knocking down the expression of H3.3 induced cell transformation, whereas ectopic expression of H3.3 attenuated arsenic-induced cell transformation. Notably, arsenic exposure also resulted in displacement of H3.3 from active promoters, enhancers, and insulator regions. These data suggest that H3.3 displacement might be central to carcinogenesis caused by polyadenylation of H3.1 mRNA upon arsenic exposure. Our findings illustrate the importance of proper histone stoichiometry in maintaining genome integrity.

PubMed ID: 32920490 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

Back
to Top