ATP-dependent chromatin remodeling shapes the long noncoding RNA landscape

Alcid, Eric A; Tsukiyama, Toshio

doi:10.1101/gad.250902.114

Cited by 49 publications

(66 citation statements)

References 60 publications

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“…Much like FACT, a chromatin remodeler that also reduces R-loop formation to enable replication fork progression through transcribed regions (Herrera-Moyano et al 2014), INO80C was reported to limit the abundance of spurious and unstable noncoding RNA transcripts (Alcid and Tsukiyama 2014). This may be related to the RNAPII eviction that we scored on HU.…”

Section: A Novel Role For Paf1c In Polymerase Evictionmentioning

confidence: 99%

“…INO80C maps to many transcription start sites in budding yeast yet also contributes to DSB repair and replication fork restart following removal of hydroxyurea (HU) (Gerhold et al 2015). Interestingly, INO80C can down-regulate transcription by repressing short-lived noncoding RNA at intergenic sites (Alcid and Tsukiyama 2014), possibly by restricting accessibility for RNA polymerase (Xue et al 2015).…”

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confidence: 99%

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Mec1, INO80, and the PAF1 complex cooperate to limit transcription replication conflicts through RNAPII removal during replication stress

et al. 2016

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Little is known about how cells ensure DNA replication in the face of RNA polymerase II (RNAPII)-mediated transcription, especially under conditions of replicative stress. Here we present genetic and proteomic analyses from budding yeast that uncover links between the DNA replication checkpoint sensor Mec1-Ddc2 (ATR-ATRIP), the chromatin remodeling complex INO80C (INO80 complex), and the transcription complex PAF1C (PAF1 complex). We found that a subset of chromatin-bound RNAPII is degraded in a manner dependent on Mec1, INO80, and PAF1 complexes in cells exposed to hydroxyurea (HU). On HU, Mec1 triggers the efficient removal of PAF1C and RNAPII from transcribed genes near early firing origins. Failure to evict RNAPII correlates inversely with recovery from replication stress: paf1Δ cells, like ino80 and mec1 mutants, fail to restart forks efficiently after stalling. Our data reveal unexpected synergies between INO80C, Mec1, and PAF1C in the maintenance of genome integrity and suggest a mechanism of RNAPII degradation that reduces transcription-replication fork collision.

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Section: A Novel Role For Paf1c In Polymerase Evictionmentioning

confidence: 99%

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confidence: 99%

Mec1, INO80, and the PAF1 complex cooperate to limit transcription replication conflicts through RNAPII removal during replication stress

et al. 2016

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“…The INO80 complex has demonstrated roles in transcription (7)(8)(9), replication (10)(11)(12), DNA damage responses (13)(14)(15)(16), telomere regulation (17), and mitotic stability (18,19). These studies exemplify the functional diversity of the INO80 complex in different pathways (20).…”

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confidence: 97%

The INO80 Complex Requires the Arp5-Ies6 Subcomplex for Chromatin Remodeling and Metabolic Regulation

Yao

King

Beckwith

et al. 2016

Molecular and Cellular Biology

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d ATP-dependent chromatin remodeling complexes are essential for transcription regulation, and yet it is unclear how these multisubunit complexes coordinate their activities to facilitate diverse transcriptional responses. In this study, we found that the conserved Arp5 and Ies6 subunits of the Saccharomyces cerevisiae INO80 chromatin-remodeler form an abundant and distinct subcomplex in vivo and stimulate INO80-mediated activity in vitro. Moreover, our genomic studies reveal that the relative occupancy of Arp5-Ies6 correlates with nucleosome positioning at transcriptional start sites and expression levels of >1,000 INO80-regulated genes. Notably, these genes are significantly enriched in energy metabolism pathways. Specifically, arp5⌬, ies6⌬, and ino80⌬ mutants demonstrate decreased expression of genes involved in glycolysis and increased expression of genes in the oxidative phosphorylation pathway. Deregulation of these metabolic pathways results in constitutively elevated mitochondrial potential and oxygen consumption. Our results illustrate the dynamic nature of the INO80 complex assembly and demonstrate for the first time that a chromatin remodeler regulates glycolytic and respiratory capacity, thereby maintaining metabolic stability. E ukaryotic genomic DNA is assembled with histones to form chromatin, a complex structure that undergoes constant dynamic reorganization in coordination with DNA-templated processes. Chromatin remodeling, an ATP-dependent mechanism by which nucleosomes are repositioned and reconstructed, is a fundamental component of chromatin manipulation and influences numerous DNA-templated pathways. Because chromatin remodelers are involved in essential cellular processes, defects in remodeling activity directly result in fitness deficiencies in lower eukaryotes, as well as developmental defects and disease in higher eukaryotes (1, 2).In particular, disruption of INO80, an evolutionarily conserved chromatin remodeling complex, results in pluripotency defects and carcinogenesis (3-6). The INO80 complex has demonstrated roles in transcription (7-9), replication (10-12), DNA damage responses (13-16), telomere regulation (17), and mitotic stability (18,19). These studies exemplify the functional diversity of the INO80 complex in different pathways (20). Moreover, they highlight the need for regulatory mechanisms that direct its activity among, and within, these processes.Ample opportunities for regulation of chromatin remodeling exist at the level of individual remodeler complex subunits. For example, different subunits of the INO80 complex are involved in DNA repair and cell cycle checkpoint responses (13, 16). Structural studies demonstrate that these subunits are components of different modules that interact with distinct domains of the S. cerevisiae Ino80 ATPase subunit (21) and thus may impart regulatory functions on ATP-dependent activities of the INO80 complex.For example, a module consisting of actin and actin-related proteins (Arps) Arp8 and Arp4 interacts with the helicase-associated...

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“…43 Therefore, the highly conserved ATP-dependent chromatin-remodeling factors may serve as global lncRNA repressors. 43 The repression of antisense lncRNAs may be a common mechanism of mRNA regulation. This view is consistent with the observation that Brg1 represses the expression of Mhrt, which is antisense to Myh7, to promote the expression of Myh7 mRNA in pathologically stressed hearts.…”

Section: Lncrna Transcription Can Be Controlled By Atp-dependent Chromentioning

confidence: 99%

“…43 These chromatinremodeling factors repress over 250 antisense lncRNAs (chromatin remodelingrepressed antisense transcripts or CRRATs) to maintain normal expression of mRNA transcripts that overlap with those antisense lncRNAs. 43 Therefore, the highly conserved ATP-dependent chromatin-remodeling factors may serve as global lncRNA repressors. 43 The repression of antisense lncRNAs may be a common mechanism of mRNA regulation.…”

Section: Lncrna Transcription Can Be Controlled By Atp-dependent Chromentioning

confidence: 99%

Long non-coding RNA and chromatin remodeling

2015

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ATP-dependent chromatin remodeling shapes the long noncoding RNA landscape

Cited by 49 publications

References 60 publications

Mec1, INO80, and the PAF1 complex cooperate to limit transcription replication conflicts through RNAPII removal during replication stress

Mec1, INO80, and the PAF1 complex cooperate to limit transcription replication conflicts through RNAPII removal during replication stress

The INO80 Complex Requires the Arp5-Ies6 Subcomplex for Chromatin Remodeling and Metabolic Regulation

Long non-coding RNA and chromatin remodeling

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