Cracking the survival code: autophagy-related histone modifications

Abstract

Modifications of histones, the chief protein components of the chromatin, have emerged as critical regulators of life and death. While the "apoptotic histone code" came to light a few years ago, accumulating evidence indicates that autophagy, a cell survival pathway, is also heavily regulated by histone-modifying proteins. In this review we describe the emerging "autophagic histone code" and the role of histone modifications in the cellular life vs. death decision.

Keywords: EHMT2/G9a; HAT; HDAC; HDM; HMT; KAT8/hMOF/MYST1; SUV420H2; histone code; histone posttranslational modifications.

Figure 1. Chromatin structure. Chromatin is made of repeating units of nucleosomes, which consist of ~147 base pairs of DNA wrapped around a histone octamer consisting of 2 copies each of the core histones H2A, H2B, H3, and H4. Linker histone H1 is positioned on top of the nucleosome core particles stabilizing higher order chromatin structure. The histones are subject to a wide variety of posttranslational modifications, primarily on their N-terminal tails, but also in their globular core region.

Figure 2. Autophagic histone modifications. Posttranslational modifications on histone tails that occur in autophagic cells are represented. These covalent modifications are added or removed by histone modifying enzymes often termed as “writers” and “erasers.” The modifications shown are discussed in the main text. ac, acetylated; me, methylated.

Figure 3. Autophagic vs. apoptotic histone codes. Overview of autophagy-related histone modifications that are also linked to apoptosis and/or carcinogenesis. Autophagy-related histone modifications display an intriguing inverse relationship to apoptosis-related histone modifications ac, acetylated; H, histone; K, lysine; me, methylated.