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Role for tyrosine phosphorylation of SUV39H1 histone methyltransferase in enhanced trimethylation of histone H3K9 via neuregulin-1/ErbB4 nuclear signaling. | LitMetric

Role for tyrosine phosphorylation of SUV39H1 histone methyltransferase in enhanced trimethylation of histone H3K9 via neuregulin-1/ErbB4 nuclear signaling.

Biochem Biophys Res Commun

Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan. Electronic address:

Published: April 2019

AI Article Synopsis

Article Abstract

Protein-tyrosine kinases transmit signals by phosphorylating their substrates in diverse cellular events. The receptor-type tyrosine kinase ErbB4, a member of the epidermal growth factor receptor subfamily, is activated and proteolytically cleaved upon ligand stimulation, and the cleaved ErbB4 intracellular domain (4ICD) is released into the cytoplasm and the nucleus. We previously showed that generation of nuclear 4ICD by neuregulin-1 (NRG-1) stimulation enhances the levels of trimethylation of histone H3 at lysine 9 (H3K9me3). However, it remains unclear how nuclear 4ICD enhances H3K9me3 levels. Here we show that the histone H3K9 methyltransferase SUV39H1 associates with NRG-1/ErbB4-mediated H3K9me3. Knockdown of SUV39H1 blocked NRG-1-mediated enhancement of the levels of H3K9me3. Nuclear 4ICD was found to phosphorylate SUV39H1 primarily at Tyr-297, -303, and -308 that are conserved among humans, mice, and flies. Furthermore, knockdown-rescue experiments showed that the unphosphorylatable SUV39H1 mutant (3 YF) was incapable of enhancing the levels of H3K9me3 upon NRG-1 stimulation. These results suggest that nuclear ErbB4 enhances H3K9me3 levels through tyrosine phosphorylation of SUV39H1 in NRG-1/ErbB4 signal-mediated chromatin remodeling.

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Source
http://dx.doi.org/10.1016/j.bbrc.2019.02.130DOI Listing

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