Histone Acetylation, Chromatin Remodelling and Nucleotide Excision Repair: Hint from the Study on MFA2 in Saccharomyces cerevisiae

Abstract

Nucleotide excision repair (NER) is a sophisticated repair pathway that the cell utilizes to remove a broad range of DNA damage to help maintain the functional integrity of the genome. In the context of DNA packaged into chromosomes it is clear that the NER machinery does not repair all regions with equal efficiency. Recently, we found after UV that histone acetylation and chromatin remodelling were activated. UV irradiation triggers genome-wide histone hyperacetylation at both histone H3 and H4. However, in nucleosomes at the repressed MFA2 promoter only histone H3, but not histone H4, is hyperacetylated following UV. This Gcn5p-mediated histone H3 hyperacetylation enables efficient NER at MFA2. Chromatin in this promoter also becomes more accessible after UV. This is not dependent on Gcn5p, yet it is partially dependent on Swi2p. In later repair times both events gradually return to the pre-UV state. The post-UV histone modifications and chromatin remodelling at the repressed MFA2 promoter do not activate MFA2 transcription, nor do they require damage recognition by Rad4p or Rad14p. These experiments indicate early events are triggered in chromatin in response to UV treatment, and they are likely needed for efficient NER.

Cyclosporin A and FK506 Inhibit IL-12p40 Production through the Calmodulin/Calmodulin-dependent Protein Kinase-activated Phosphoinositide 3-Kinase in Lipopolysaccharide-stimulated Human Monocytic Cells

“…It is not clear why the JNK pathway failed to compensate for LPS-induced IL-12p40 production in the presence of inhibitors specific for the calcium pathway. In addition to signal transduction pathways, molecular mechanisms controlling gene expression involve chromatin remodeling and DNA methylation (67)(68)(69). Understanding the status of promoter methylation and chromatin remodeling may elucidate the mechanisms underlying the involvement of distinct signaling pathways controlling IL-12p40 transcription.…”

HIV-1 Nef Inhibits Lipopolysaccharide-induced IL-12p40 Expression by Inhibiting JNK-activated NFκB in Human Monocytic Cells

“…The observations that nef inhibited IL-12p40 transcription in the presence of functional AP-1 suggests that AP-1 in the presence of dysfunctional NFB may not be able to drive LPS-induced IL-12p40 transcription further suggesting a potential cooperation between the two factors. Besides signal transduction pathways, molecular mechanisms controlling gene expression involve chromatin remodeling and DNA methylation (63). In addition to the inhibition of JNK and NFB, intracellular nef may inhibit IL-12p40 transcription by altering the status of promoter methylation, and chromatin remodeling.…”

Histone variant Htz1 promotes histone H3 acetylation to enhance nucleotide excision repair in Htz1 nucleosomes

“…More recently, direct evidence of roles for histone modifications and chromatin remodelling in NER has started to emerge. We previously showed that histone H3 acetylation by Gcn5 is activated in the repressed MFA2 promoter after UV irradiation in S. cerevisiae (40,41). This UV-induced histone H3 hyperacetylation is necessary for the efficient repair of UV-induced CPDs in this locus.…”