The elongata mutants identify a functional Elongator complex in plants with a role in cell proliferation during organ growth

Abstract

The key enzyme for transcription of protein-encoding genes in eukaryotes is RNA polymerase II (RNAPII). The recruitment of this enzyme during transcription initiation and its passage along the template during transcription elongation is regulated through the association and dissociation of several complexes. Elongator is a histone acetyl transferase complex, consisting of six subunits (ELP1-ELP6), that copurifies with the elongating RNAPII in yeast and humans. We demonstrate that point mutations in three Arabidopsis thaliana genes, encoding homologs of the yeast Elongator subunits ELP1, ELP3 (histone acetyl transferase), and ELP4 are responsible for the phenotypes of the elongata2 (elo2), elo3, and elo1 mutants, respectively. The elo mutants are characterized by narrow leaves and reduced root growth that results from a decreased cell division rate. Morphological and molecular phenotypes show that the ELONGATA (ELO) genes function in the same biological process and the epistatic interactions between the ELO genes can be explained by the model of complex formation in yeast. Furthermore, the plant Elongator complex is genetically positioned in the process of RNAPII-mediated transcription downstream of Mediator. Our data indicate that the Elongator complex is evolutionarily conserved in structure and function but reveal that the mechanism by which it stimulates cell proliferation is different in yeast and plants.Arabidopsis ͉ histone acetyl transferase complex ͉ leaf development ͉ RNA polymerase II

TheArabidopsis thalianaHomolog of YeastBRE1Has a Function in Cell Cycle Regulation during Early Leaf and Root Growth

“…The weaker phenotype of the hub1-4 and hub1-3 mutants compared with that of hub1-1 could be due to the genetic background (Col versus Ler) because a less severe hub1-1 phenotype was also observed in the F2 mapping population (mixed Col/Ler background). A similar observation of stronger phenotypes in Ler than in Col backgrounds had already been observed for other leaf mutants (Horiguchi et al, 2005;Nelissen et al, 2005).…”

“…A significantly high number of genes differentially expressed in hub1-1 were related to cell cycle (24 genes) and cytokinesis (31 genes). These two classes of differentially regulated genes were not present in microarray data sets of the elongata class of narrow leaf mutants (Nelissen et al, 2005) analyzed in the same experiment (D. Fleury, unpublished data). Because of the proliferation defect observed in hub1-1 leaves, we focused our analysis on these two classes of genes.…”

“…The intrinsic leaf size is determined by the number of cells produced by cell division activities during the early stages of primordium formation (Mizukami and Fischer, 2000). A group of genes have been reported to affect leaf shape and size by regulating cell numbers (Mizukami and Fischer, 2000;Nelissen et al, 2003Nelissen et al, , 2005Horiguchi et al, 2005). However, another group of genes affect cell division, leaving organ growth relatively unaffected because of a compensatory effect by cell expansion The yellow to orange color of the circles correspond to the level of significance of the overrepresented GO category from 0.05 and below according to a multiple t test with false discovery rate-corrected P value.…”

“…The availability of a collection of 94 leaf mutant loci originating from an ethyl methanesulfonate mutagenesis program (Berná et al, 1999) is an important resource to determine the genetic control of leaf growth. Many mutated genes from this collection are being cloned and their function in leaf growth analyzed in detail (Pé rez-Pé rez et al, 2004;Nelissen et al, 2005). The histone monoubiquitination1 mutant, hub1-1 (previously designated ang4-1), belongs to the angusta class of recessive mutants that consist of four loci characterized by reduced leaf size and narrow laminae (Berná et al, 1999;Robles and Micol, 2001).…”

Deregulated expression of pro-survival and pro-apoptotic p53-dependent genes upon Elongator deficiency in colon cancer cells

“…Elongator yeast mutants (elp phenotypes) have slower growth adaptation and temperature sensitivity at 39 8C [5]. The Elongata mutants of Arabidopsis thaliana, which have point mutations in genes coding for the yeast Elongator subunit Elp1, Elp3 and Elp4, are characterized by reduced root growth due to decreased cell division rate, which supports a role for Elongator in cell proliferation in plants [16].…”