Histone deacetylation and DNA methylation are associated with gene silencing. Compared to DNA methylation, little is known about histone deacetylation and plant gene silencing. We have identified a gene encoding putative histone deacetylase (HD1) in Arabidopsis, a homolog of pleiotropic transcriptional regulator in yeast and mouse. Expression of constitutive antisense AtHD1 (CASH) caused dramatic reduction in endogenous AtHD1 transcription, resulting in accumulation of acetylated histones, notably tetra-acetylated H4. Reduction in AtHD1 expression and AtHD1 production and changes in acetylation profiles were associated with developmental pleiotropy. Some of the phenotypes could be attributed to ectopic expression of tissue-specific genes (e.g., SUPERMAN). No changes in genomic DNA methylation were detected in the transgenic plants. These results suggest that AtHD1 is a global regulator, which controls gene expression during development through DNA-sequence independent mechanisms in plants.

Recently, we have isolated a T-DNA insertion line in exon 2 of AtHD1, resulting in a null allele (athd1-t1). Both athd1-t1 and CASH lines display increased levels of histone acetylation and similar developmental abnormalities, which are heritable in the presence of anti-sense AtHD1 or in the progeny of homozygous (athd1-t1/athd1-t1) plants. No additional epigenetic effects are observed in subsequent selfing generations. Furthermore, when the athd1-t1/athd1-t1 plants are crossed to wild-type plants, the pleiotropic developmental abnormalities are immediately restored in the F1 hybrids, which is correlated with AtHD1 expression and reduction of histone H4 Lys12 acetylation. The abnormal developmental phenotype segregates as a recessive trait in the F2 population. Unlike the situation with the stable code of DNA and histone methylation, developmental changes induced by histone deacetylase defects are immediately reversible, probably through the restoration of a reversible histone acetylation code needed for the normal control of gene regulation and development.

We will uncover the target genes that are affected by disrupting AtHD1 expression and determine whether the expression of target genes is directly or indirectly associated with changes in histone acetylation profiles. Histone deacetylases are encoded by multi-gene families. We are interested in understanding of the functional divergence between members of the gene family and their specificity in histone deacetylation and gene regulation