PAF1 complex component Leo1 helps recruit
            <i>Drosophila</i>
            Myc to promoters

Gerlach, J; Furrer, Michael; Gallant, Maria; Birkel, Dirk; Baluapuri, Apoorva; Wolf, Elmar; Gallant, Peter

doi:10.1073/pnas.1705816114

Cited by 29 publications

(27 citation statements)

References 72 publications

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“…In yeast, scPAF1C has been reported to be non-essential 19,20 . In flies, dLeo1 is not essential to get viable adults 49 . In mice, mPAF1 +/− or mLEO1 +/− heterozygosity yields no obvious abnormalities, although mPAF1 −/− or mLEO1 −/− null animals show pre-weaning lethality 50 .…”

Section: Discussionmentioning

confidence: 99%

Toxic expanded GGGGCC repeat transcription is mediated by the PAF1 complex in C9orf72-associated FTD

et al. 2019

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An expanded (G4C2)30+ repeat within C9orf72 is the most prominent mutation in familial FTD and ALS. Through an unbiased, large-scale screen in (G4C2)49-expressing Drosophila we identify the CDC73/PAF1 complex (PAF1C), a transcriptional regulator of RNAPII, as a suppressor of G4C2-associated toxicity. Depletion of PAF1C reduces RNA and GR-dipeptide production from (G4C2)30+ transgenes. Interestingly, dPAF1C components, dPaf1 and dLeo1 appear selective for transcription of long, toxic repeat expansions, but not shorter, non-toxic expansions. In yeast, scPAF1C components regulate expression of both sense and anti-sense repeats. PAF1C is upregulated upon expression of (G4C2)30+ in flies and mice. hPaf1 is also upregulated in C9+ -derived cells and its heterodimer partner, hLeo1, binds C9 + repeat chromatin. In C9+ FTD, hPAF1 and hLEO1 are upregulated and their expression positively correlates with expression of repeat-containing C9orf72 transcripts. These data indicate that PAF1C activity is an important factor for transcription of the long, toxic repeat in C9+ FTD.

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Section: Discussionmentioning

confidence: 99%

Toxic expanded GGGGCC repeat transcription is mediated by the PAF1 complex in C9orf72-associated FTD

et al. 2019

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“…Although it has been well proven that MYC is able to bind the E-box in vitro with a high affinity, the sequence-specific interaction is not sufficient for recruiting MYC to its chromatin target sites (16). Recently, WDR5 and the PAF1 complex subunit LEO1 were shown to interact with MYC and facilitate its recruitment to target genes in various systems (17)(18)(19). Here, we found that the DNA binding factor ZFP281 directly recruits MYC to active gene promoters in mouse ES cells.…”

Section: Discussionmentioning

confidence: 99%

ZFP281 Recruits MYC to Active Promoters in Regulating Transcriptional Initiation and Elongation

Luo

Liu

Xie

et al. 2019

Molecular and Cellular Biology

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The roles of the MYC transcription factor in transcriptional regulation have been studied intensively. However, the general mechanism underlying the recruitment of MYC to chromatin is less clear. Here, we found that the Krüppel-like transcription factor ZFP281 plays important roles in recruiting MYC to active promoters in mouse embryonic stem cells. At the genome scale, ZFP281 is broadly associated with MYC, and the depletion of ZFP281 significantly reduces the levels of MYC and RNA polymerase II at the ZFP281- and MYC-cobound genes. Specially, we found that recruitment is required for the regulation of the Lin28a oncogene and pri-let-7 transcription. Our results therefore suggest a major role of ZFP281 in recruiting MYC to chromatin and the integration of ZFP281 and the MYC/LIN28A/Let-7 loop into a multilevel circuit.

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“…First, MYC may recruit CDK9 to promoters to mediate pause release (Rahl et al., 2010). Second, MYC transfers the Pol II-associated factor 1 (PAF1) complex onto Pol II upon ubiquitin-mediated degradation of MYC (Gerlach et al., 2017, Jaenicke et al., 2016). This latter observation raised the possibility that MYC influences the assembly of Pol II with transcription elongation factors, thus changing the behavior of Pol II during productive elongation.…”

Section: Introductionmentioning

confidence: 99%

MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation

et al. 2019

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PAF1 complex component Leo1 helps recruit Drosophila Myc to promoters

Cited by 29 publications

References 72 publications

Toxic expanded GGGGCC repeat transcription is mediated by the PAF1 complex in C9orf72-associated FTD

Toxic expanded GGGGCC repeat transcription is mediated by the PAF1 complex in C9orf72-associated FTD

ZFP281 Recruits MYC to Active Promoters in Regulating Transcriptional Initiation and Elongation

MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation

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