A Novel Histone Acetyltransferase Is an Integral Subunit of Elongating RNA Polymerase II Holoenzyme

Abstract

The elongator complex is a major component of the RNA polymerase II (RNAPII) holoenzyme responsible for transcriptional elongation in yeast. Here we identify Elp3, the 60-kilodalton subunit of elongator/RNAPII holoenzyme, as a highly conserved histone acetyltransferase (HAT) capable of acetylating core histones in vitro. In vivo, ELP3 gene deletion confers typical elp phenotypes such as slow growth adaptation, slow gene activation, and temperature sensitivity. These results suggest a role for a novel, tightly RNAPII-associated HAT in transcription of DNA packaged in chromatin.

Elp3 drives Wnt-dependent tumor initiation and regeneration in the intestine

“…Elp3 sequence harbors motifs found in the GNAT family of histone acetyltransferases (HATs; Otero et al, 1999;Wittschieben et al, 1999;Kim et al, 2002) and a radical S-adenosylmethionine (SAM) domain at the N-terminal region that includes a FeS cluster critical for Elongator integrity (Greenwood et al, 2009). Elongator promotes transcriptional elongation in the nucleus through histone H3 acetylation but also, as a cytoplasmic complex, in translational efficiency by adding 5-methoxycarbonylmethyl (mcm 5 ) and 5-carbamoylmethyl (ncm 5 ) groups on uridines at the wobble position of some tRNAs Winkler et al, 2002;Huang et al, 2005;Close et al, 2006;Esberg et al, 2006;Bauer et al, 2012;Lin et al, 2013).…”

Histone Hyperacetylation in the Coding Region of Chromatin Undergoing Transcription in SV40 Minichromosomes Is a Dynamic Process Regulated Directly by the Presence of RNA Polymerase II

“…The observation that more hyperacetylated H4 and H3 were associated with RNAPII than was present in other in other regions of the transcribed chromatin has not been previously reported. However, these results have been predicted (31,30) based upon the observation that RNAPII can be found with piggybacked HATs (5,32) . Similarly, the presence of unacetylated forms of H4 and H3 at sites not occupied by RNAPII, which resulted from HDAC activity, has not previously been observed, although their existence has also been suggested.…”

“…In this regard the p300 may be substituting for the PCAF or "elongator" cofactors, which have previously been shown to bind to RNAPII and are also capable of hyperacetylating H4 and H3 (32,25,34) . While this is the first report that p300 is bound to RNAPII in actively chromatin undergoing transcription, p300 has been shown to bind to RNAPII (32,25,34) . It is also possible that other HAT activities including PCAF or elongator are associated with the RNAPII in transcribing SV40 chromatin.…”

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].…”

“…Elongator requires the scaffold IKK-associated protein (IKAP)/ELP1/hELP1 for assembling into a functional complex [4]. Moreover, Elp3, the catalytic subunit, harbours motifs found in the GNAT family of histone acetyltransferases (HATs) [5] and is essential for the ability of Elongator to target histone H3 in vitro [2,3,6] and in vivo [7]. These observations combined with reports showing an association of Elongator with several nascent RNAs in yeast [8] and with the preferential recruitment of Elongator to the transcribed regions of human genes [9][10][11], strongly support a role for Elongator in transcriptional elongation.…”