ATX1 functions as an activator of homeotic genes, like Trithorax in animal systems. The histone methylating activity of the ATX1-SET domain argues that the molecular basis of these effects is the ability of ATX1 to modify chromatin structure. Our results suggest a conservation of trxG function between the animal and plant kingdoms despite the different structural nature of their targets.

Gene duplication followed by functional specialization is a potent force in the evolution of biological diversity. A comparative study of two highly conserved duplicated genes, ARABIDOPSIS TRITHORAX-LIKE PROTEIN1 (ATX1) and ATX2, revealed features of both partial redundancy and of functional divergence. Although structurally similar, their regulatory sequences have diverged, resulting in distinct temporal and spatial patterns of expression of the ATX1 and ATX2 genes. We found that ATX2 methylates only a limited fraction of nucleosomes and that ATX1 and ATX2 influence the expression of largely nonoverlapping gene sets. Even when coregulating shared targets, ATX1 and ATX2 may employ different mechanisms. Most remarkable is the divergence of their biochemical activities: both proteins methylate K4 of histone H3, but while ATX1 trimethylates it, ATX2 dimethylates it. ATX2 and ATX1 provide an example of separated K4 di from K4 trimethyltransferase activity.

The Arabidopsis homolog of trithorax, ATX1, regulates numerous functions in Arabidopsis beyond the homeotic genes. Here, we identified genome-wide targets of ATX1 and showed that ATX1 is a receptor for a lipid messenger, phosphatidylinositol 5-phosphate, PI5P. PI5P negatively affects ATX1 activity, suggesting a regulatory pathway connecting lipid-signaling with nuclear functions. We propose a model to illustrate how plants may respond to stimuli (external or internal) that elevate cellular PI5P levels by altering expression of ATX1-controlled genes.epigenetic regulation ͉ lipid signaling P roteins of the trithorax family activate the early homeotic genes that regulate animal development and embryonic pattern formation (1, 2). A major difference in the developmental process in plants is that organ formation is not restricted to the embryonic state, differentiation and organogenesis occurring throughout the lifespan of the organism. In plants, as in animals, homeosis is a consequence of a mutation of a homeotic gene. Usually, homeotic genes encode transcription factors. Unlike the animal counterparts, however, many of the plant homeotic genes belong to the MADSbox family (3). Despite the difference in structure, plant homeotic genes, like animal counterparts, are controlled by factors belonging to the trithorax family (4). Mutation of the Arabidopsis homolog of trithorax, ATX1, causes numerous developmental defects in the formation, placement, and identity of flower organs: Petals (second-whorl organs) were seen to develop stems, a third-whorl feature; stamens (third-whorl organs) developed ovules, a fourthwhorl characteristic (4).The signature feature of all trithorax proteins is the presence of the highly conserved SET [SuVar (3-9)-E(z)-trithorax] domain. The discovery that the SET domain peptides carry histone methyltransferase activity (5) provided critical evidence that chromatinmodifying activities function as epigenetic regulators. Certain lysines at the histone tails can be either acetylated or methylated, creating recognition sites for cellular repressive or activating complexes (6). SET domains of the trithorax family can methylate lysine 4 of histone H3, a modification associated with transcriptional activation (7). The SET domain of ATX1 has histone H3-K4 methyltransferase activity and can activate expression of Arabidopsis genes (4, 8). Thus, biochemical and genetic evidence define ATX1 as a functional homolog of the animal trithorax genes.Regulation of homeotic genes is only one possible role for trithorax (9, 10). In Arabidopsis, atx1 mutants displayed stem-, root-, and leaf-growth defects, indicating that the plant homolog of trithorax has pleiotropic roles (4). By whole genome expression profiling, we determined that Ϸ1,700 genes changed robust expression as a result of ATX1 loss of function. The altered expression of these genes provides a probable molecular basis underlying the pleiotropic functions of ATX1.The most important result of the study reported here is the finding that ATX1 can specifi...

Plants respond to environmental stresses by altering transcription of genes involved in the response. The chromatin modifier ATX1 regulates expression of a large number of genes; consequently, factors that affect ATX1 activity would also influence expression from ATX1-regulated genes. Here, we demonstrate that dehydration is such a factor implicating ATX1 in the plant's response to drought. In addition, we report that a hitherto unknown Arabidopsis gene, At3g10550, encodes a phosphoinositide 3'-phosphatase related to the animal myotubularins (AtMTM1). Myotubularin activities in plants have not been described and herein, we identify an overlapping set of genes co-regulated by ATX1 and AtMTM under drought conditions. We propose that these shared genes represent the ultimate targets of partially overlapping branches of the pathways of the nuclear ATX1 and the cytoplasmic AtMTM1. Our analyses offer first genome-wide insights into the relationship of an epigenetic factor and a lipid phosphatase from the other end of a shared drought responding pathway in Arabidopsis.