A Chromatin-remodeling Protein Is a Component of Fission Yeast Mediator

Khorosjutina, Olga; Wanrooij, Paulina H.; Walfridsson, Julian; Szilágyi, Zsolt; Zhu, Xuefeng; Baraznenok, Vera; Ekwall, Karl; Gustafsson, Claes M.

doi:10.1074/jbc.m110.153858

Cited by 18 publications

(14 citation statements)

References 36 publications

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“…This is a CHD1 ATP-dependent chromatin-remodeling factor, which has been shown to interact directly with the centromere during DNA replication in early S phase (11,58). Interestingly, we have recently demonstrated that Hrp1 is also a transient component of the Mediator complex in fission yeast (27). This observation raises the interesting possibility that Mediator not only regulates ncRNA transcription in the central core region but also affects the activity of Hrp1 at specific centromeric nucleosomes; i.e., Mediator can effect CENP-A Cnp1 incorporation by partially independent mechanisms.…”

Section: Discussionmentioning

confidence: 98%

Mediator Promotes CENP-A Incorporation at Fission Yeast Centromeres

Carlsten

Szilágyi

Liu

et al. 2012

Molecular and Cellular Biology

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dAt Schizosaccharomyces pombe centromeres, heterochromatin formation is required for de novo incorporation of the histone H3 variant CENP-A Cnp1 , which in turn directs kinetochore assembly and ultimately chromosome segregation during mitosis. Noncoding RNAs (ncRNAs) transcribed by RNA polymerase II (Pol II) directs heterochromatin formation through not only the RNA interference (RNAi) machinery but also RNAi-independent RNA processing factors. Control of centromeric ncRNA transcription is therefore a key factor for proper centromere function. We here demonstrate that Mediator directs ncRNA transcription and regulates centromeric heterochromatin formation in fission yeast. Mediator colocalizes with Pol II at centromeres, and loss of the Mediator subunit Med20 causes a dramatic increase in pericentromeric transcription and desilencing of the core centromere. As a consequence, heterochromatin formation is impaired via both the RNAi-dependent and -independent pathways, resulting in loss of CENP-A Cnp1 from the core centromere, a defect in kinetochore function, and a severe chromosome segregation defect. Interestingly, the increased centromeric transcription observed in med20⌬ cells appears to directly block CENP-A Cnp1 incorporation since inhibition of Pol II transcription can suppress the observed phenotypes. Our data thus identify Mediator as a crucial regulator of ncRNA transcription at fission yeast centromeres and add another crucial layer of regulation to centromere function.

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Section: Discussionmentioning

confidence: 98%

Mediator Promotes CENP-A Incorporation at Fission Yeast Centromeres

Carlsten

Szilágyi

Liu

et al. 2012

Molecular and Cellular Biology

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“…Mammalian Chd1 binds with higher avidity to H3K4me3 chromatin in vitro. Moreover, Chd1 is recruited to chromatin via Mediator (Khorosjutina et al, 2010; Lin et al, 2011) and its transcriptional stimulatory effect is largely on H3K4me3 chromatin in vitro. Thus, Chd1 is an H3K4me3 and Mediator stimulated event, whereas EP400 recruitment is neither, so we did not pursue Chd1’s role in variant chromatin transcription.…”

Section: Discussionmentioning

confidence: 99%

EP400 Deposits H3.3 into Promoters and Enhancers during Gene Activation

Pradhan¹,

Su²,

Yen³

et al. 2016

Molecular Cell

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Gene activation in metazoans is accompanied by the presence of histone variants H2AZ and H3.3 within promoters and enhancers. It is not known however what protein deposits H3.3 into chromatin or whether variant chromatin plays a direct role in gene activation. Here we show that chromatin containing acetylated H2AZ and H3.3 stimulates transcription in vitro. Analysis of the Pol II pre-initiation complex on immobilized chromatin templates revealed that the E1A Binding Protein p400 (EP400) was bound preferentially to and required for transcription stimulation by acetylated double-variant chromatin. EP400 also stimulated H2AZ/H3.3 deposition into promoters and enhancers and influenced transcription in vivo at a step downstream of the Mediator complex. EP400 efficiently exchanged recombinant histones H2A and H3.1 with H2AZ and H3.3, respectively, in a chromatin- and ATP-stimulated manner in vitro. Our data reveal that EP400 deposits H3.3 into chromatin alongside H2AZ and contributes to gene regulation after PIC assembly.

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“…Recent studies have demonstrated an interaction between Mediator and the cohesin complex to loop the enhancer and promoter regions for gene activation (Kagey et al, 2010). Mediator has also been shown to interact with several cofactors or their complexes (Ebmeier and Taatjes, 2010; Johnson et al, 2002; Khorosjutina et al, 2010; Wallberg et al, 2003); interestingly, most of them have been shown to play roles in mRNA processing, such as Brm (Batsche et al, 2006), CHD (Sims et al, 2007), SRC (Auboeuf et al, 2002), PGC-1 (Monsalve et al, 2000), and TFIID (Dantonel et al, 1997). Here we identified interactions between Mediator and mRNA processing factors, which links the Mediator complex with the splicing machinery (Figure 6K).…”

Section: Discussionmentioning

confidence: 99%

Mediator Complex Regulates Alternative mRNA Processing via the MED23 Subunit

et al. 2012

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SUMMARY Mediator complex is an integrative hub for transcriptional regulation. Here we show that Mediator regulates alternative mRNA processing via its Med23 subunit. Combining tandem affinity purification and mass spectrometry, we identified a number of mRNA processing factors that bind to a soluble recombinant Mediator subunit MED23 but not to several other Mediator components. One of these factors, hnRNP L, specifically interacts with MED23 in vitro and in vivo. Consistently, Mediator partially colocalizes with hnRNP L and the splicing machinery in the cell. Functionally Med23 regulates a subset of hnRNP L-targeted alternative splicing (AS) and alternative cleavage and polyadenylation (APA) events as shown by minigene reporters and exon array analysis. ChIP-seq analysis revealed that Med23 can regulate hnRNP L occupancy at their co-regulated genes. Taken together, these results demonstrate a crosstalk between Mediator and the splicing machinery, providing a molecular basis for coupling mRNA processing to transcription.

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A Chromatin-remodeling Protein Is a Component of Fission Yeast Mediator

Cited by 18 publications

References 36 publications

Mediator Promotes CENP-A Incorporation at Fission Yeast Centromeres

Mediator Promotes CENP-A Incorporation at Fission Yeast Centromeres

EP400 Deposits H3.3 into Promoters and Enhancers during Gene Activation

Mediator Complex Regulates Alternative mRNA Processing via the MED23 Subunit

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