The Chromatin Remodeling Factor CSB Recruits Histone Acetyltransferase PCAF to rRNA Gene Promoters in Active State for Transcription Initiation

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.

HDAC inhibition improves autophagic and lysosomal function to prevent loss of subcutaneous fat in a mouse model of Cockayne syndrome

“…Accordingly, it has been shown that UV-and hypoxiamediated acetylation of histone H4 at the promoters of certain responsive genes is impaired in CSB-HF, and that this is due to defective recruitment of the HAT p300 to the acetylation site (19,20). A similar function of CSB has also been demonstrated for another HAT, p300/CBP-associated factor (PCAF), because it is recruited to rRNA promoters in a CSB-dependent manner to enable transcription initiation (50). We believe that the impact of CSB on acetylation of nuclear targets might be relevant for its role in regulating chromatin remodeling (51,52).…”

Cockayne syndrome group B protein regulates DNA double‐strand break repair and checkpoint activation

“…For example, in human cells, trimethylation of H3K36 has been suggested to promote DNA end resection and repair of DSBs via HR (Aymard et al , ; Pfister et al , ) and modification of H3K9 has been implicated in the DSB response in heterochromatin that is preferentially repaired by HR (Chiolo et al , ). CSB has been found, in different contexts, to associate with numerous chromatin modifying and remodeling factors such as NuRD (Xie et al , ), SMARCA5 (Aydin et al , ) as well as histone methyltransferase G9A (Yuan et al , ) and acetyltransferase PCAF (Shen et al , ), while the yeast homolog of CSB, Rad26, has been reported to genetically interact with the H3K36 methyltransferase SET2 (Jha & Strahl, ).…”

“…The EMBO Journal Role of CSB in DNA double-strand break repair Nicole L Batenburg et al HR (Chiolo et al, 2011). CSB has been found, in different contexts, to associate with numerous chromatin modifying and remodeling factors such as NuRD (Xie et al, 2012), SMARCA5 (Aydin et al, 2014) as well as histone methyltransferase G9A (Yuan et al, 2007) and acetyltransferase PCAF (Shen et al, 2013), while the yeast homolog of CSB, Rad26, has been reported to genetically interact with the H3K36 methyltransferase SET2 (Jha & Strahl, 2014). Although transcription inhibition did not abolish the impairment of CSB-KO cells in IR-induced Rad51 foci formation and ATM activation, it abrogated the accumulation of CSB at sites of DNA DSBs.…”

The Core Subunit of A Chromatin-Remodeling Complex, ZmCHB101, Plays Essential Roles in Maize Growth and Development

“…Chromatin assembly and remodeling are believed to be epigenetic switches responsible for the on/off state of rRNA genes34353637. In interphase nuclei, most of 45 S rRNA genes are compacted into heterochromatic chromocenters and the florescent in situ hybridization (FISH) signals manifest as compacted spots in WT maize (Fig.…”