Epigenetic transcriptional memory

Abstract

Organisms alter gene expression to adapt to changes in environmental conditions such as temperature, nutrients, inflammatory signals, and stress (Gialitakis et al. in Mol Cell Biol 30:2046-2056, 2010; Conrath in Trends Plant Sci 16:524-531, 2011; Avramova in Plant J 83:149-159, 2015; Solé et al. in Curr Genet 61:299-308, 2015; Ho and Gasch in Curr Genet 61:503-511, 2015; Bevington et al. in EMBO J 35:515-535, 2016; Hilker et al. in Biol Rev Camb Philos Soc 91:1118-1133, 2016). In some cases, organisms can "remember" a previous environmental condition and adapt to that condition more rapidly in the future (Gems and Partridge 2008). Epigenetic transcriptional memory in response to a previous stimulus can produce heritable changes in the response of an organism to the same stimulus, quantitatively or qualitatively altering changes in gene expression (Brickner et al. in PLoS Biol, 5:e81, 2007; Light et al. in Mol Cell 40:112-125, 2010; in PLoS Biol, 11:e1001524, 2013; D'Urso and Brickner in Trends Genet 30:230-236, 2014; Avramova in Plant J 83:149-159, 2015; D'Urso et al. in Elife. doi: 10.7554/eLife.16691 , 2016). The role of chromatin changes in controlling binding of poised RNAPII during memory is conserved from yeast to humans. Here, we discuss epigenetic transcriptional memory in different systems and our current understanding of its molecular basis. Our recent work with a well-characterized model for transcriptional memory demonstrated that memory is initiated by binding of a transcription factor, leading to essential changes in chromatin structure and allowing binding of a poised form of RNA polymerase II to promote the rate of future reactivation (D'Urso et al. in Elife. doi: 10.7554/eLife.16691 , 2016).

Keywords: Chromatin; Environmental response; Epigenetics; Histone methylation; Mediator; Memory; Nuclear pore complex; Transcription; Transcription factor.

Figure 1. Conserved and universal features of epigenetic transcriptional memory

A. Chromatin changes during memory. Histones within the repressed promoter are hypoacetylated and unmethylated. Upon transcriptional activation, nucleosomes become acetylated (green circles) and tri-methylated (red circles) on histone H3, lysine 4 by the Set1/COMPASS writer. Upon repression, memory is initiated by the binding of a specific transcription factor (TF), leading to remodeling of the writer to generate H3K4me2. This mark recruits the SET3C reader complex, which promotes the persistence of H3K4me2 possibly by a positive feedback with the remodeled writer complex. B. Mediator-dependent poising. Active transcription is associated with the preinitiation complex, including Mediator lacking Cdk8 and the Cdk7/TFIIK kinase, which phosphorylates serine 5 of the RNAPII CTD to stimulate initiation. Upon repression, memory is initiated by the specific binding of a Transcription Factor (TF), leading to remodeling of Mediator to recruit Cdk8 and potentially excluding Cdk7/TFIIK. Cdk8⁺ Mediator promotes recruitment of poised RNAPII during memory, bypassing the rate-limiting step in future activation.