Cell cycle-regulated oscillator coordinates core histone gene transcription through histone acetylation

Abstract

DNA replication occurs during the synthetic (S) phase of the eukaryotic cell cycle and features a dramatic induction of histone gene expression for concomitant chromatin assembly. Ectopic production of core histones outside of S phase is toxic, underscoring the critical importance of regulatory pathways that ensure proper expression of histone genes. Several regulators of histone gene expression in the budding yeast Saccharomyces cerevisiae are known, yet the key oscillator responsible for restricting gene expression to S phase has remained elusive. Here, we show that suppressor of Ty (Spt)10, a putative histone acetyltransferase, and its binding partner Spt21 are key determinants of S-phase-specific histone gene expression. We show that Spt21 abundance is restricted to S phase in part by anaphase promoting complex Cdc20-homologue 1 (APC Cdh1) and that it is recruited to histone gene promoters in S phase by Spt10. There, Spt21-Spt10 enables the recruitment of a cascade of regulators, including histone chaperones and the histone-acetyltransferase general control nonderepressible (Gcn) 5, which we hypothesize lead to histone acetylation and consequent transcription activation.

Low expression of microRNA-1908 predicts a poor prognosis for patients with ovarian cancer

“…SIRT2 is a NAD-dependent deacetylase that is involved in a number of cellular processes, including cell proliferation, death, senescence and stress responses (17,18). PONDL1 is a transcription factor; however, its function remains unclear (19). SBF1 encodes a member of the protein-tyrosine phosphatase family; this protein contains a guanine nucleotide exchange factor domain, necessary for its role in cell growth and differentiation (16).…”

Regulation of DNA replication-coupled histone gene expression

“…Such process requires histone synthesis and their assembly into DNA to be efficiently coupled to DNA synthesis [ 2 – 4 ]. Based on their expression pattern, histone genes are generally classified into two classes [ 5 , 6 ]. The first class comprises DNA replication tightly regulated histones whose expression level is high during DNA replication but reduced after DNA replication is completed.…”

“…At the end of S phase or DNA synthesis is interrupted, cells turned off histone transcription and histone mRNA levels declined rapidly [ 8 ]. The second class of histones is composed of histone variants that are expressed at a relatively low level throughout the cell cycle, and are therefore regulated in a DNA replication-independent manner [ 6 ]. Maintaining a stable and balanced histone pool is of vital importance for appropriate gene regulation, cell cycle progression and genome stability.…”

Characterisation of functional domains in fission yeast Ams2 that are required for core histone gene transcription

“…In budding yeast, expression of the zinc finger protein Spt10 is independent of the cell cycle. In contrast, Spt10’s binding partner, Spt21, is expressed in a cell cycle-dependent fashion, with peaks of expression occurring during S phase25. We hypothesise that Ams2 and Teb1 may play roles in fission yeast equivalent to the respective functions of Spt10 and Spt21 in budding yeast.…”