Regulation of histone gene transcription in yeast

Abstract

Histones are the primary protein component of chromatin, the mixture of DNA and proteins that packages the genetic material in eukaryotes. Large amounts of histones are required during the S phase of the cell cycle when genome replication occurs. However, ectopic expression of histones during other cell cycle phases is toxic; thus, histone expression is restricted to the S phase and is tightly regulated at multiple levels, including transcriptional, post-transcriptional, translational, and post-translational. In this review, we discuss mechanisms of regulation of histone gene expression with emphasis on the transcriptional regulation of the replication-dependent histone genes in the model yeast Saccharomyces cerevisiae.

Fig. 1

Core histone expression during the yeast cell cycle. RD core histone genes are expressed exclusively in late G1 and S phase of the cell cycle, in parallel with the replication of DNA. Outside of the S phase, histone expression is toxic; therefore, cells tightly restrict histone production to the S phase. See text for details

Fig. 2

Repression/activation model for the regulation of RD histone gene transcription in yeast. Upper panel a repressed HTA1–HTB1 gene promoter. Here, HIR recruits Rtt106, RSC, Asf1, and Yta7 in order to generate a repressive chromatin structure (nucleosomes with Rtt106-assembled H3/H4) at promoters. NEG also CCR (cell cycle control region), UAS upstream activating sequence and TATA (TATA-box). A repressive chromatin structure prevents the recruitment of the basal transcription machinery and RNAPII. See text for details. Lower panel the HTA1–HTB1 promoter in an active state. Rtt109-dependent incorporation of H3 acetylated at K56 (H3K56ac) enables recruitment of SWI/SNF, which generates a nucleosome-depleted promoter, enabling RNAPII recruitment. Other unidentified HATs are very likely involved in this process as well (see text for details). S phase forms of CDK1 (S-CDK) then phosphorylate Yta7 causing its eviction from promoters (which is tracked by the RSC), which is important for efficient promoter escape and transcript-elongation by RNAPII. Spt10 and Spt21 have important roles in these processes as well, but their molecular functions remain to be revealed