Abstract
The promoters of poised rRNA genes (rDNA) are marked by both euchromatic and heterochromatic histone modifications and are associated with two transcription factors, UBF and SL1 that nucleate transcription complex formation. Active rRNA genes contain only euchromatic histone modifications and are loaded with all components of transcriptional initiation complex including RNA polymerase I. Coupled with histone acetylation and RNA polymerase I targeting, poised promoters can be converted to active ones by ATP-dependent chromatin remodeling factor CSB for initiation of rDNA transcription. However, it is not clear how dynamic histone modifications induce the assembly of polymerase I transcription initiation complex to active promoters during such conversion. Here we show that a complex consisting of CSB, RNA polymerase I and histone acetyltransferase PCAF is present at the rDNA promoters in active state. CSB is required for the association of PCAF with rDNA, which induces acetylation of histone H4 and histone H3K9. Overexpression of CSB promotes the association of PCAF with rDNA. Knockdown of PCAF leads to decreased levels of H4ac and H3K9ac at rDNA promoters, prevents the association of RNA polymerase I and inhibits pre-rRNA synthesis. The results demonstrate that CSB recruits PCAF to rDNA, which allows histone acetylation that is required for the assembly of polymerase I transcription initiation complex during the transition from poised to active state of rRNA genes, suggesting that CSB and PCAF play cooperative roles to establish the active state of rRNA genes by histone acetylation.
Highlights
Ribosomal genes are transcribed by transcription machinery of RNA polymerase I (Pol I)
We found that hyperacetylation of histones H4 and H3K9 in active rDNA promoters was induced by histone acetyltransferase PCAF
PCAF was required for acetylation of H4 and H3K9, and these modifications were required for the loading of Pol I to rDNA promoters and activation of Pol I transcription
Summary
Ribosomal genes are transcribed by transcription machinery of RNA polymerase I (Pol I). Active promoters are unmethylated and exhibit euchromatic features, silent promoters are methylated and exhibit heterochromatic histone modifications, and poised promoters are unmethylated and marked by hypoacetylated histone H4 and trimethylated H3K4 (H3K4me3) [5]. Initiation of rRNA gene transcription requires the conversion from poised configuration to active state that is controlled by the chromatin remodeler protein, CSB (Cockayne syndrome group B). As a member of the complex comprising Pol I, TFIIH and basal Pol I transcription factors [14], CSB interacts with histone methyltransferase G9a, which methylates histone H3 on lysine 9 (H3K9me2) in the pre-rRNA coding region facilitating transcription elongation [15]
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