title: Lysine acetylation controls local protein conformation by influencing proline isomerization.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Françoise S
authors.initials: FS
authors.lastname: Howe
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Ivan
authors.initials: I
authors.lastname: Boubriak
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sale
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Anitha
authors.initials: A
authors.lastname: Nair
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: David
authors.initials: D
authors.lastname: Clynes
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Grijzenhout
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Struan C
authors.initials: SC
authors.lastname: Murray
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Ronja
authors.initials: R
authors.lastname: Woloszczuk
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: jane.mellor@bioch.ox.ac.uk.
authors.forename: Jane
authors.initials: J
authors.lastname: Mellor
mesh_terms: D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D044127:Epigenesis, Genetic; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D007536:Isomerism; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D011392:Proline / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D002843:Chromatin; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D011392:Proline; D008239:Lysine