Proline
| Autor: | Françoise S, Howe, Jane, Mellor |
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| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Molecular Cell |
| ISSN: | 2311-2638 |
| Popis: | Summary Gene transcription responds to stress and metabolic signals to optimize growth and survival. Histone H3 (H3) lysine 4 trimethylation (K4me3) facilitates state changes, but how levels are coordinated with the environment is unclear. Here, we show that isomerization of H3 at the alanine 15-proline 16 (A15-P16) peptide bond is influenced by lysine 14 (K14) and controls gene-specific K4me3 by balancing the actions of Jhd2, the K4me3 demethylase, and Spp1, a subunit of the Set1 K4 methyltransferase complex. Acetylation at K14 favors the A15-P16trans conformation and reduces K4me3. Environmental stress-induced genes are most sensitive to the changes at K14 influencing H3 tail conformation and K4me3. By contrast, ribosomal protein genes maintain K4me3, required for their repression during stress, independently of Spp1, K14, and P16. Thus, the plasticity in control of K4me3, via signaling to K14 and isomerization at P16, informs distinct gene regulatory mechanisms and processes involving K4me3. Graphical Abstract Highlights • H3K14 acetylation influences cis-trans isomerization at the H3A15-P16 peptide bond • H3A15-P16trans is associated with H3K14ac and reduced global H3K4me3 • A15-P16cis-trans isomerization balances K4me3 (Set1/Spp1) and demethylation (Jhd2) • K4me3 on RPGs is largely Spp1- and K14/P16-insensitive while ESR genes are dependent The histone H3 tail is intrinsically disordered yet extensively modified. Howe et al. show that lysine 14 acetylation influences cis-trans isomerization at the alanine 15-proline 16 peptide bond to control gene-specific lysine 4 trimethylation. Lysine acetylation in proximity to proline residues may seed alternative conformations in disordered regions, allowing interactions with different effector proteins. |
| Databáze: | OpenAIRE |
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