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The chromatin remodeling factor CSB recruits histone acetyltransferase PCAF to rRNA gene promoters in active state for transcription initiation.

Shen M, Zhou T, Xie W, Ling T, Zhu Q, Zong L, Lyu G, Gao Q, Zhang F, Tao W - PLoS ONE (2013)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Cell Proliferation and Differentiation, National Key Laboratory of Protein Engineering and Plant Gene Engineering, College of Life Science, Peking University, Beijing, China.

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.

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Schematic models for the role of PCAF and CSB in rRNA transcription.Deacetylation of H4 and H3K9 are associated with poised rDNA promoters, whereas acetylation of H4 and H3K9 are restricted to rDNA promoters in active state. After conversion of poised rDNA promoters to active ones, PCAF is recruited to active state of rRNA promoters by CSB, and induces acetylation of histones to promote association of RNA polymerase I with rDNA promoters, thereby facilitating the initiation of rDNA transcription.
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pone-0062668-g006: Schematic models for the role of PCAF and CSB in rRNA transcription.Deacetylation of H4 and H3K9 are associated with poised rDNA promoters, whereas acetylation of H4 and H3K9 are restricted to rDNA promoters in active state. After conversion of poised rDNA promoters to active ones, PCAF is recruited to active state of rRNA promoters by CSB, and induces acetylation of histones to promote association of RNA polymerase I with rDNA promoters, thereby facilitating the initiation of rDNA transcription.

Mentions: In this study, we found that hyperacetylation of histones H4 and H3K9 in active rDNA promoters was induced by histone acetyltransferase PCAF. In addition, CSB interacted with PCAF, and knockdown of CSB reduced the binding of PCAF to rDNA promoters. Overexpression of CSB increased the level of PCAF binding to rDNA, indicating that PCAF was recruited to rDNA by CSB. Furthermore, CSB mediated the interaction between PCAF and Pol I. Knockdown of either CSB or PCAF impaired the association of Pol I with rDNA and inhibited pre-rRNA synthesis. Moreover, 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. Finally, sequential ChIP revealed that CSB and PCAF occupied the same region on active rDNA promoter sequences. Based on these data, we propose that the transition from poised rDNA promoters to active ones is accompanied with the recruitment of PCAF by CSB, resulting in acetylation of histones and assembly of Pol I transcription initiation complex (Figure 6). Our results demonstrated that CSB and PCAF participate in the conversion of rRNA genes from poise to active state by histone acetylation.


The chromatin remodeling factor CSB recruits histone acetyltransferase PCAF to rRNA gene promoters in active state for transcription initiation.

Shen M, Zhou T, Xie W, Ling T, Zhu Q, Zong L, Lyu G, Gao Q, Zhang F, Tao W - PLoS ONE (2013)

Schematic models for the role of PCAF and CSB in rRNA transcription.Deacetylation of H4 and H3K9 are associated with poised rDNA promoters, whereas acetylation of H4 and H3K9 are restricted to rDNA promoters in active state. After conversion of poised rDNA promoters to active ones, PCAF is recruited to active state of rRNA promoters by CSB, and induces acetylation of histones to promote association of RNA polymerase I with rDNA promoters, thereby facilitating the initiation of rDNA transcription.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3646882&req=5

pone-0062668-g006: Schematic models for the role of PCAF and CSB in rRNA transcription.Deacetylation of H4 and H3K9 are associated with poised rDNA promoters, whereas acetylation of H4 and H3K9 are restricted to rDNA promoters in active state. After conversion of poised rDNA promoters to active ones, PCAF is recruited to active state of rRNA promoters by CSB, and induces acetylation of histones to promote association of RNA polymerase I with rDNA promoters, thereby facilitating the initiation of rDNA transcription.
Mentions: In this study, we found that hyperacetylation of histones H4 and H3K9 in active rDNA promoters was induced by histone acetyltransferase PCAF. In addition, CSB interacted with PCAF, and knockdown of CSB reduced the binding of PCAF to rDNA promoters. Overexpression of CSB increased the level of PCAF binding to rDNA, indicating that PCAF was recruited to rDNA by CSB. Furthermore, CSB mediated the interaction between PCAF and Pol I. Knockdown of either CSB or PCAF impaired the association of Pol I with rDNA and inhibited pre-rRNA synthesis. Moreover, 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. Finally, sequential ChIP revealed that CSB and PCAF occupied the same region on active rDNA promoter sequences. Based on these data, we propose that the transition from poised rDNA promoters to active ones is accompanied with the recruitment of PCAF by CSB, resulting in acetylation of histones and assembly of Pol I transcription initiation complex (Figure 6). Our results demonstrated that CSB and PCAF participate in the conversion of rRNA genes from poise to active state by histone acetylation.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Cell Proliferation and Differentiation, National Key Laboratory of Protein Engineering and Plant Gene Engineering, College of Life Science, Peking University, Beijing, China.

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.

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