Lysine Acetylation Controls Local Protein Conformation by Influencing Proline Isomerization

Françoise S Howe,Ivan Boubriak,Matthew J Sale,Anitha Nair,David Clynes,Anne Grijzenhout,Struan C Murray,Ronja Woloszczuk,Jane Mellor

doi:10.1016/j.molcel.2014.07.004

Abstract

SummaryGene 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.

Highlights

The packaging of eukaryotic genomes into chromatin has fundamental effects on gene expression but how this is brought about still remains poorly understood
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
Environmental stressinduced genes are most sensitive to the changes at K14 influencing H3 tail conformation and K4me3

Summary

Introduction

The packaging of eukaryotic genomes into chromatin has fundamental effects on gene expression but how this is brought about still remains poorly understood. Histone proteins are highly conserved and are subject to many different posttranslational modifications (PTMs) including acetylation and methylation (Rando and Winston, 2012) These modifications can influence nucleosome occupancy and position as well as the recruitment of a wide range of effector proteins implicated in a variety of cellular processes. Genome-wide mapping studies show that modification patterns are correlated with both gene structure and gene activity, often showing characteristic distributions on active or repressed genes (Liu et al, 2005; Pokholok et al, 2005) One such modification is Set1-dependent methylation of lysine 4 on histone H3 (K4), present in most eukaryotes at active or potentially active genes (Santos-Rosa et al, 2002). Methylated K4 is influenced by the modification state at distant residues on nucleosomal histones including H2Bub and K14ac promoting, and H3R2me and K4ac antagonizing K4me and K4me to varying extents (Briggs et al, 2002; Guillemette et al, 2011; Kirmizis et al, 2007; Maltby et al, 2012; Nakanishi et al, 2008)

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Discussion

Conclusion