Arabidopsis histone deacetylase 6: a green link to RNA silencing

Abstract

Epigenetic reprogramming is at the base of cancer initiation and progression. Generally, genome-wide reduction in cytosine methylation contrasts with the hypermethylation of control regions of functionally wellestablished tumor suppressor genes and many other genes whose role in cancer biology is not yet clear. While insight into mechanisms that induce aberrant cytosine methylation in cancer cells is just beginning to emerge, the initiating signals for analogous promoter methylation in plants are well documented. In Arabidopsis, the silencing of promoters requires components of the RNA interference machinery and promoter double-stranded RNA (dsRNA) to induce a repressive chromatin state that is characterized by cytosine methylation and histone deacetylation catalysed by the RPD3-type histone deacetylase AtHDA6. Similar mechanisms have been shown to occur in fission yeast and mammals. This review focuses on the connections between cytosine methylation, dsRNA and AtHDA6-controlled histone deacetylation during promoter silencing in Arabidopsis and discusses potential mechanistic similarities of these silencing events in cancer and plant cells.

HISTONE DEACETYLASE6 Interacts with FLOWERING LOCUS D and Regulates Flowering in Arabidopsis

“…Genome-wide gene expression analysis using the Affymetrix GeneChip indicates that down-regulation of HDA6 affected genes involved in a variety of biological processes. In addition to genes involved in flowering, genes involved in gene silencing and stress responses were also affected in hda6 mutants, supporting multiple functions of HDA6 (Aufsatz et al, 2007;Wu et al, 2008;Chen et al, 2010;Earley et al, 2010). We found that the expression of two genes encoding AGO proteins, AGO5 and AGO3, was up-regulated in hda6 mutants.…”

“…7C). In addition, a subset of transposons was upregulated in axe1-5 and HDA6-RNAi plants (Table I), supporting a role of HDA6 in maintaining the stability of transposons (Aufsatz et al, 2007). Nine transposons analyzed all showed a correlation between qRT-PCR and microarray data (Fig.…”

“…Besides histone modifications, DNA methylation is also associated with gene-silencing mechanisms in eukaryotic organisms. Recent studies suggest that HDA6 is required for maintaining cytosine methylation (Aufsatz et al, 2007;Earley et al, 2010). Based on genomic transcriptional analysis, we demonstrate that HDA6 regulates transposon expression.…”

“…In addition to FLC, MAF4, and MAF5, two additional MADS box genes, AGL37 and AT1G59930, were also up-regulated in axe1-5 and HDA6-RNAi plants. HDA6 is implicated in gene silencing and stress responses (Aufsatz et al, 2007;Wu et al, 2008). Therefore, we investigated the expression of genes related to gene silencing and stress responses by qRT-PCR.…”

“…The AGO proteins are involved in RNA-silencing processes that also involve 21-to 25-nucleotide short RNAs cleaved from double-stranded RNAs by the RNaseIII enzyme Dicer (Baumberger and Baulcombe, 2005). It is suggested that HDA6 plays an important role in RNAimediated heterochromatin formation (Aufsatz et al, 2007;Earley et al, 2010). Up-regulation of AGO5 and AGO3 in hda6 mutants suggests that HDA6 may be involved in RNAi-mediated gene silencing by regulating the expression of AGO-like genes.…”