The Fission Yeast HIRA Histone Chaperone Is Required for Promoter Silencing and the Suppression of Cryptic Antisense Transcripts

Abstract

The assembly of nucleosomes by histone chaperones is an important component of transcriptional regulation. Here, we have assessed the global roles of the HIRA histone chaperone in Schizosaccharomyces pombe. Microarray analysis indicates that inactivation of the HIRA complex results in increased expression of at least 4% of fission yeast genes. HIRA-regulated genes overlap with those which are normally repressed in vegetatively growing cells, such as targets of the Clr6 histone deacetylase and silenced genes located in subtelomeric regions. HIRA is also required for silencing of all 13 intact copies of the Tf2 long terminal repeat (LTR) retrotransposon. However, the role of HIRA is not restricted to bona fide promoters, because HIRA also suppresses noncoding transcripts from solo LTR elements and spurious antisense transcripts from cryptic promoters associated with transcribed regions. Furthermore, the HIRA complex is essential in the absence of the quality control provided by nuclear exosome-mediated degradation of illegitimate transcripts. This suggests that HIRA restricts genomic accessibility, and consistent with this, the chromosomes of cells lacking HIRA are more susceptible to genotoxic agents that cause double-strand breaks. Thus, the HIRA histone chaperone is required to maintain the protective functions of chromatin.

HIRA, a Conserved Histone Chaperone, Plays an Essential Role in Low-dose Stress Response via Transcriptional Stimulation in Fission Yeast

“…5A). This basal up-regulation of some CESR genes is consistent with previous reports (26,38). In general, all the genes examined showed smaller differences in transcriptional levels between the non-stress condition and the priming stress condition in the mutant cells compared with the wild-type cells.…”

“…A strong correlation (r 2 Ͼ 0.998) was noted between slm9⌬ and hip1⌬ samples under all conditions (supplemental Fig. S4), consistent with the previously reported strong correlation of gene expression between slm9⌬ and hip1⌬ cells under the normal conditions (38).…”

“…We also found that in the crosstolerance, the expression levels of stress-responsive genes under the severe stress were augmented when the cells were exposed to the priming stress. Although the fission yeast HIRA has been shown to be implicated in gene silencing and the heterochromatin assembly (26,38,40,56), our results showed that the fission yeast HIRA is required for the transcriptional activation of stress-responsive genes under the low-dose stress conditions. Therefore, HIRA would regulate transcription both positively and negatively.…”

“…The ectopic expression of HIRA in human cells also represses the transcription of histones (37). In the fission yeast, HIRA is required for the suppression of Tf2 long terminal repeat retrotransposons, normally repressed genes, or cryptic antisense transcripts (38). Consistent with its repressive role in transcription, HIRA also functions in heterochromatin assembly and silencing.…”

Myogenic transcriptional activation of MyoD mediated by replication-independent histone deposition

“…Chromatin remodeling factor CHD1, which belongs to the chromodomain family of SNF2-like adenosine triphosphatases, is also responsible for H3.3 incorporation into the male pronucleus, presumably in couple with HIRA (10). Besides, HIRA is involved in the formation of senescence-associated heterochromatic foci (SAHF) (11) and the maintenance of gene silencing (12)(13)(14). Formation of SAHF is driven by HIRA and another H3/H4 chaperone Asf1a and involves repression of proliferation-promoting genes.…”