%0 Journal Article
%T The relationship between transcription initiation RNAs and CCCTC-binding factor (CTCF) localization
%A Ryan J Taft
%A Peter G Hawkins
%A John S Mattick
%A Kevin V Morris
%J Epigenetics & Chromatin
%D 2011
%I BioMed Central
%R 10.1186/1756-8935-4-13
%X In the present work, we show that tiRNAs are commonly found at genomic CCCTC-binding factor (CTCF) binding sites in human and mouse, and that CTCF sites that colocalize with RNAPII are highly enriched for tiRNAs. To directly investigate the relationship between tiRNAs and CTCF we examined tiRNAs originating near the intronic CTCF binding site in the human tumor suppressor gene, p21 (cyclin-dependent kinase inhibitor 1A gene, also known as CDKN1A). Inhibition of CTCF-proximal tiRNAs resulted in increased CTCF localization and increased p21 expression, while overexpression of CTCF-proximal tiRNA mimics decreased CTCF localization and p21 expression. We also found that tiRNA-regulated CTCF binding influences the levels of trimethylated H3K27 at the alternate upstream p21 promoter, and affects the levels of alternate p21 (p21alt) transcripts. Extending these studies to another randomly selected locus with conserved CTCF binding we found that depletion of tiRNA alters nucleosome density proximal to sites of tiRNA biogenesis.Taken together, these data suggest that tiRNAs modulate local epigenetic structure, which in turn regulates CTCF localization.In addition to mRNAs, it is now clear that most eukaryotic genic loci generate a complex network of overlapping short (<200) and long non-protein coding RNA (ncRNA) species [1-3]. This growing catalog of ncRNAs includes a host of small RNA (sRNA) transcripts proximal to transcription start sites (TSSs) [4], some of which are capped [5] or associate with polycomb repressive complex (PCR2) components [6,7]. We have recently described a set of nuclear localized dominantly 18 nucleotide tiny RNAs that are generated from regions immediately downstream of TSSs and conserved across metazoa but absent in fungi and plants [8,9]. We have previously suggested that these transcription initiation RNAs (tiRNAs) may be connected to epigenetic regulation in light of the fact that (i) they originate from the same position relative to the +1 nuc
%U http://www.epigeneticsandchromatin.com/content/4/1/13