Transcription factors dynamically control the spatial organization of the yeast genome

Abstract

In yeast, inducible genes such as INO1, PRM1 and HIS4 reposition from the nucleoplasm to nuclear periphery upon activation. This leads to a physical interaction with nuclear pore complex (NPC), interchromosomal clustering, and stronger transcription. Repositioning to the nuclear periphery is controlled by cis-acting transcription factor (TF) binding sites located within the promoters of these genes and the TFs that bind to them. Such elements are both necessary and sufficient to control positioning of genes to the nuclear periphery. We have identified 4 TFs capable of controlling the regulated positioning of genes to the nuclear periphery in budding yeast under different conditions: Put3, Cbf1, Gcn4 and Ste12. In each case, we have defined the molecular basis of regulated relocalization to the nuclear periphery. Put3- and Cbf1-mediated targeting to nuclear periphery is regulated through local recruitment of Rpd3(L) histone deacetylase complex by transcriptional repressors. Rpd3(L), through its histone deacetylase activity, prevents TF-mediated gene positioning by blocking TF binding. Many yeast transcriptional repressors were capable of blocking Put3-mediated recruitment; 11 of these required Rpd3. Thus, it is a general function of transcription repressors to regulate TF-mediated recruitment. However, Ste12 and Gcn4-mediated recruitment is regulated independently of Rpd3(L) and transcriptional repressors. Ste12-mediated recruitment is regulated by phosphorylation of an inhibitor called Dig2, and Gcn4-mediated gene targeting is up-regulated by increasing Gcn4 protein levels. The ability to control spatial position of genes in yeast represents a novel function for TFs and different regulatory strategies provide dynamic control of the yeast genome through different time scales.

Lamina-Associated Domains: Links with Chromosome Architecture, Heterochromatin, and Gene Repression

“…In yeast, which does not have a NL, there is extensive evidence that NPCs can interact with specific genes as well as telomeres (Ibarra and Hetzer, 2015; Randise-Hinchliff and Brickner, 2016). In metazoans, the picture is more complex.…”

Nuclear pore complexes and regulation of gene expression

“…Targeting to the nuclear periphery for several yeast genes has been shown to rely on cis-DNA sequences in their promoters known as Gene Recruitment Sequences (GRSs) (recently reviewed in [27]) (Figure 1). Interestingly, several GRSs have been shown to represent binding sites for transcription factors which ultimately mediate gene-relocation [21].…”

“…Interestingly, several GRSs have been shown to represent binding sites for transcription factors which ultimately mediate gene-relocation [21]. For INO1 it was identified that NPC-tethering is mediated by the transcription factors Put3 [28] and Cbf1 [27], which do not directly regulate the activity of this gene. Conversely, the Ste12 and Gcn4 transcription factors required for repositioning of PRM1 and HIS4 also regulate the activity of these genes [21].…”

“…Conversely, the Ste12 and Gcn4 transcription factors required for repositioning of PRM1 and HIS4 also regulate the activity of these genes [21]. Yet, the activation domain of Gcn4 is dispensable for gene repositioning [27]. These findings indicate that the transcription factors involved in gene positioning not necessarily need to regulate the expression of the gene, separating the processes of gene positioning and transcriptional regulation.…”

Light behind the curtain: photoregulation of nuclear architecture and chromatin dynamics in plants

“…Hierarchical and spatial distribution of chromosomes, chromatin domains and coregulated gene loci is tightly regulated through association with specific nuclear structures and protein complexes. Studies in yeast, fruit flies, humans and plants indicate that the position of a gene within the nucleus can influence its transcriptional potency (Gibcus & Dekker, 2013;Liu & Weigel, 2015;Randise-Hinchliff & Brickner, 2016). Major developmental reprogramming events are usually accompanied by repositioning of gene loci towards the nuclear interior, the periphery or proximally to chromocentres depending on the species and the associated proteins that will determine the extent of gene activation or silencing (Takizawa et al, 2008;Feng et al, 2014;Bourbousse et al, 2015;Wang et al, 2015;Randise-Hinchliff & Brickner, 2016;Rodriguez-Granados et al, 2016).…”