The two gene pairs encoding H2A and H2B play different roles in the Saccharomyces cerevisiae life cycle.

Abstract

We have isolated Saccharomyces cerevisiae mutants bearing deletions of one or the other of the two divergently transcribed gene pairs encoding H2A and H2B. The deletions produced diverse effects on the yeast life cycle. Deletion of TRT1, one of the H2A-H2B gene pair sets, affected mitotic growth, sporulation, spore germination, the heat shock response, and exit from the stationary phase; deletion of TRT2, the other H2A-H2B gene pair set, had negligible effects on these same processes. Using a genetic complementation assay, we found that the differential effects of the deletions could be attributed to two features of the gene sets: first, the expression of the TRTI gene pair, but not the TRT2 gene pair, could compensate for the absence of its partner; second, the protein subtypes encoded by the two gene pairs appear to have different functions in the heat shock response.Most DNA in eucaryotic chromosomes is associated with four core histones in a structure known as the nucleosome (18). It has long been assumed, but until recently never directly demonstrated, that nucteosomes are essential for chromosomes to function properly. The discovery that Saccharomyces cerevisiae contains only two genes for each core histone has made it possible to assess the in vivo function of nucleosomes by genetic analysis (10). Three points have emerged from such studies. First, H2A and H2B are essential proteins in yeast, since strains bearing frameshift mutations in both copies of the genes encoding H2A (HTAI and HTA2) or the genes encoding H2B (HTBI and HTB2) are inviable (5,15,25). Second, H2B may be required for mitosis, since a strain bearing a conditionally expressed HTB2 gene arrests late in the cell cycle when the synthesis of H2B is turned off (6). Finally, the maintenance of normal H2A-H2B dimer stoichiometry is a prerequisite for proper chromosome segregation, since overexpression of the genes for H2A and H2B decreases the fidelity of mitotic chromosome transmission (19).The last work (19) also suggested how the cell may regulate the formation of nucleosomes. Chromosome loss was increased only when H2A and H2B were jointly overexpressed and not when either protein was overexpressed individually. This result implies that the H2A-H2B dimer, and not H2A or H2B alone, regulates nucleosome formation in vivo. A regulatory role for the H2A-H2B dimer may also be reflected in the genomic arrangement of the HTA and HTB genes in yeast. These genes are located in two divergently transcribed TRT loci (TRTJ and TRT2), each of which contains one HTA gene and one HTB gene (Fig. 1A and B) (10). We have shown that the HTA and HTB genes at each locus are expressed at the same time during the cell cycle and that the genes at TRT1 are regulated by the same promoter elements (9,11,21). This observation, coupled with the apparent regulatory role of the H2A-H2B dimer, suggests that it may be more accurate to consider the TRT loci rather than the individual HTA and HTB genes as the regulatory units for H2A and H2B production. * Corresponding author...

A single copy of linker H1 genes is enough for proliferation of the DT40 chicken B cell line, and linker H1 variants participate in regulation of gene expression

“…Namely, in both mutants several cellular proteins newly appeared or increased, and some other proteins disappeared or decreased quantitatively. These results together suggested that the H1 variants (and the core histone variants) play individual particular roles in certain biological events including gene expression, like those in yeasts (Norris & Osley 1987;Norris et al 1988;Carr et al 1994;Hirschhorn et al 1995;Megee et al 1995), Xenopus (Bouvet et al 1994), and Tetrahymena thermophila (Shen & Gorovsky 1996).…”

“…Many in vivo studies have been performed on the new nature of core histones-in addition to the vital role in chromatin organization mentioned above, especially in yeasts (Hereford et al 1982;Meeks-Wagner & Hartwell 1986;Norris & Osley 1987;Osley & Lycan 1987;Clark-Adams et al 1988;Norris et al 1988;Grunstein 1990;Carr et al 1994;Hirschhorn et al 1995)because gene replacement experiments on them can be carried out easily. Moreover, it has been reported that in Saccharomyces cerevisiae, the deletion of H4 N-terminal residues 4-23 or mutagenesis of the acetylatable lysines in this region decreases the activation of the GAL1 promoter, while the deletion of N-terminal residues 4-15 of H3 or the mutagenesis of the acetylatable lysines causes a hyperactivation of GAL1 (Fisher-Adams & Grunstein 1995).…”

Regulation of Histone Gene Expression in Budding Yeast

“…Thus, a post-transcriptional dosage compensation mechanism is active, acting through changes in mRNA turnover rates. The HTA2-HTB2 locus does not show dosage compensation: deletion of HTA1-HTB1 leads to a severe growth phenotype, but deletion of HTA2-HTB2 is compensated for by increased HTA1-HTB1 transcription (Norris and Osley 1987). HHT1-HHF1 and HHT2-HHF2 do not compensate for one another (Cross and Smith 1988;Smith and Stirling 1988).…”

“…The other two loci, HTA1-HTB1 and HTA2-HTB2, encode almost identical H2A and H2B proteins (Hereford et al 1979). Initially, it was thought that HTA1-HTB1 and HTA2-HTB2 could also substitute for one another, although it was clear that HTA1-HTB1 is not equivalent to HTA2-HTB2 because deletion of the former is associated with a significant growth phenotype, whereas deletion of the latter has no obvious effect (Norris and Osley 1987). However, it is now clear that hta1-htb1D cells survive only if the HTA2-HTB2 locus has been duplicated and that this duplication can occur in the S288C strain background but not in the W303 background because the latter lacks one of two Ty1 elements required for the duplication (Libuda and Winston 2006).…”

Yeast adenylate kinase is transcribed constitutively from a promoter in the short intergenic region to the histone H2A‐1 gene

“…The genes for the histones H2A-1 and H2B-1 (HTA1 and HTB1, respectively) are clustered on chromosome IV of the yeast genome [10,11]. Their transcription is correlated with the progression of the cell cycle and turned on for only a short period of time at the beginning of the S-phase [12][13][14][15].…”