Regulation of Histone Gene Expression in Budding Yeast

Abstract

We discuss the regulation of the histone genes of the budding yeast Saccharomyces cerevisiae. These include genes encoding the major core histones (H3, H4, H2A, and H2B), histone H1 (HHO1), H2AZ (HTZ1), and centromeric H3 (CSE4). Histone production is regulated during the cell cycle because the cell must replicate both its DNA during S phase and its chromatin. Consequently, the histone genes are activated in late G1 to provide sufficient core histones to assemble the replicated genome into chromatin. The major core histone genes are subject to both positive and negative regulation. The primary control system is positive, mediated by the histone gene-specific transcription activator, Spt10, through the histone upstream activating sequences (UAS) elements, with help from the major G1/S-phase activators, SBF (Swi4 cell cycle box binding factor) and perhaps MBF (MluI cell cycle box binding factor). Spt10 binds specifically to the histone UAS elements and contains a putative histone acetyltransferase domain. The negative system involves negative regulatory elements in the histone promoters, the RSC chromatin-remodeling complex, various histone chaperones [the histone regulatory (HIR) complex, Asf1, and Rtt106], and putative sequence-specific factors. The SWI/SNF chromatin-remodeling complex links the positive and negative systems. We propose that the negative system is a damping system that modulates the amount of transcription activated by Spt10 and SBF. We hypothesize that the negative system mediates negative feedback on the histone genes by histone proteins through the level of saturation of histone chaperones with histone. Thus, the negative system could communicate the degree of nucleosome assembly during DNA replication and the need to shut down the activating system under replication-stress conditions. We also discuss post-transcriptional regulation and dosage compensation of the histone genes.

Topology and Control of the Cell-Cycle-Regulated Transcriptional Circuitry

“…The extent to which the overlap is reflected in coordinate or differential regulation is only beginning to be understood (see below) (Bean et al 2005;Eser et al 2011;de Oliveira et al 2012;Smolka et al 2012;Travesa and Wittenberg 2012;. Finally, many potential and actual binding sites have been identified in promoters that do not appear to promote cell-cycle periodicity but may, in some cases, have functional consequences (Iyer et al 2001;Horak et al 2002;Bean et al 2005; also see Haber 2012; Eriksson et al 2012).…”

“…Histone genes are regulated by an, as yet, poorly understood transcriptional regulatory mechanism involving SBF, Spt10, histone chaperones, and other factors. That S phase cluster has been recently reviewed by Eriksson et al (2012) and will not be discussed further here. The second, much larger, cluster of genes expressed during S phase is that regulated by Hcm1 ( Figure 3).…”

“…Interestingly, in a two-step process, Rpd3(L) dissociates from G2/M gene promoters at the onset of S phase in a manner that depends upon Cln/CDK and, only then, does the combined activation of Clb2/CDK and Cdc5 promote eviction of a nucleosome from those promoters and binding of Ndd1 to Fkh2. Recent studies describing a role for histone chaperones and chromatin boundary proteins in chromatin remodeling at the histone gene cluster are reviewed elsewhere (Eriksson et al 2012). Together, these studies suggest both direct and indirect roles for cluster-specific transcription factors in the recruitment and regulation of chromatin modifying and remodeling proteins.…”

“…This general topic has been extensively reviewed (Bähler 2005;Wittenberg and Reed 2005;McInerny 2011) and indepth reviews covering specific transcription factor families and cell-cycle-regulated gene clusters have been presented (Murakami et al 2010;Cross et al 2011;Eriksson et al 2012). We will introduce the constituents and regulatory logic of the cell-cycle transcriptional circuitry with discussion weighted toward more recent contributions.…”

A Novel Approach for Studying Histone H1 Function in Vivo

“…In budding yeast, core histones are subject to negative autoregulation (Gunjan et al 2006;Eriksson et al 2012). Autoregulation also maintains constant levels of core histones in Drosophila (McKay et al 2015).…”