%0 Journal Article
%T Knockdown of menin affects pre-mRNA processing and promoter fidelity at the interferon-gamma inducible IRF1 gene
%A Lauren B Auriemma
%A Shaili Shah
%A Lara M Linden
%A Melissa A Henriksen
%J Epigenetics & Chromatin
%D 2012
%I BioMed Central
%R 10.1186/1756-8935-5-2
%X RNAi-mediated knockdown of MEN1 alters the H3K4 dimethylation and H3 acetylation profiles, and the localization of histone deacetylase 3, at IRF1. While MEN1 knockdown does not impact the rate of transcription, IRF1 heteronuclear transcripts become enriched in MEN1-depleted cells. The processed mRNA and translated protein product are concomitantly reduced, and the antiviral state is attenuated. Additionally, the transcription start site at the IRF1 promoter is disrupted in the MEN1-depleted cells. The H3K4 demethylase, lysine specific demethylase 1, is also associated with IRF1, and its inhibition alters H3K4 methylation and disrupts the transcription start site as well.Taken together, the data indicate that MEN1 contributes to STAT1-activated gene expression in a novel manner that includes defining the transcription start site and RNA processing.Eukaryotic gene expression is regulated by dynamic nuclear signaling events that occur at the chromatin template and include post-translational modification of the histone proteins, via methylation, phosphorylation, acetylation and ubiquitination. Depending upon the position of a lysine residue in the histone amino acid sequence, histone lysine methylation is associated with either an activated or a repressed transcriptional state [1,2]. For example, methylation of K27 and K9 of histone H3 and K20 of histone H4 correlates with transcriptionally silent regions, while methylation of K4, K36 and K79 of histone H3 is associated with activated chromatin. Lysine methylation is further elaborated by the degree of methylation, such that mono-, di- or trimethylation of the same lysine residue can affect chromatin structure differently.In Saccharomyces cerevisiae, a single complex containing the histone methyltransferase (HMT) Set1 is responsible for the methylation of histone H3K4. In mammalian systems, six homologs of Set1 contribute to different Set1-like HMT complexes to accomplish this modification [1,2]. The Set1A/Set1B complex
%K HDACs
%K histone
%K JAK-STAT
%K lysine methylation
%K transcription
%U http://www.epigeneticsandchromatin.com/content/5/1/2