High impact information on ELP3

• Here, we show that cells lacking the histone acetyltransferases Gcn5 and Elp3 have widespread and severe histone H3 hypoacetylation in chromatin [1].
• In vivo, ELP3 gene deletion confers typical elp phenotypes such as slow growth adaptation, slow gene activation, and temperature sensitivity [2].
• Here we show that mutations that impair the in vitro HAT activity of Elp3 confer typical elp phenotypes such as temperature sensitivity [3].
• Because concomitant active site alterations in Elp3 and Gcn5 are sufficient to confer severe phenotypes, the redundancy must be specifically related to the HAT activity of these complexes [3].
• Here we show that, in contrast to the isolated Elp3 subunit, the activity of intact Elongator complex is directed specifically toward the amino-terminal tails of histone H3 and H4, and that Elongator can acetylate both core histones and nucleosomal substrates [4].

Biological context of ELP3

• Mutagenesis of ELP3/TOT3, the Elongator histone acetyltransferase (HAT) gene, revealed that zymocin sensitivity could be uncoupled from Elongator wild-type function, indicating that TOT interacts genetically with zymocin [5].
• The central region of Elp3 shares significant sequence homology to the Radical SAM superfamily [6].
• These results imply a link between the acetylation of specific sites in nucleosomal histones and the regulation of transcription elongation by human Elp3 [7].

Associations of ELP3 with chemical compounds

• Our results provide biochemical support to the hypothesis that Elp3 does indeed contain the Fe4S4 cluster which characterizes the Radical SAM superfamily and binds SAM, suggesting that Elp3, in addition to its HAT activity, has a second as yet uncharacterized catalytic function [6].
• The Elongator subunit Elp3 contains a Fe4S4 cluster and binds S-adenosylmethionine [6].

Other interactions of ELP3

• In contrast, histones in genes previously shown to require the histone acetyltransferases GCN5 and ELP3 for normal transcription do not lose DNA contacts, but do become acetylated as a result of transcription [8].
• However, a variety of genetic experiments comparing the effects of mutation in ELP3 and KTI12 alone and in combination with other transcription factor mutations clearly demonstrate a significant functional overlap between Elongator and Kti12 in vivo [9].
• Transfer RNA immunoprecipitation experiments showed that the Elp1 and Elp3 proteins specifically coprecipitate a tRNA susceptible to formation of an mcm5 side chain, indicating a direct role of Elongator in tRNA modification [10].
• Elp2 and Elp4 were largely dispensable for the association of Elongator with nascent RNA transcript in vivo.In contrast, Elongator-RNA interaction requires the Elp3 protein [11].
• The inviability of ctk1 elp3 double mutants can be rescued by expression of an Elp3 mutant that has retained its ability to form the Elongator complex but has severely diminished histone acetyltransferase activity, suggesting that the functional overlap between CTDK-I and Elongator is in assembly of RNA polymerase II elongation complexes [12].

Analytical, diagnostic and therapeutic context of ELP3

• By using chromatin immunoprecipitation, we show that the levels of multiply acetylated histone H3 and H4 in chromatin are decreased in vivo in yeast cells lacking ELP3 [4].

References