Functional Analysis of Bre1p, an E3 Ligase for Histone H2B Ubiquitylation, in Regulation of RNA Polymerase II Association with Active Genes and Transcription in Vivo

Sen, Rwik; Lahudkar, Shweta; Durairaj, Geetha; Bhaumik, Sukesh R.

doi:10.1074/jbc.m113.450403

Cited by 19 publications

(27 citation statements)

References 57 publications

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“…Likewise, the loss of Paf1p impairs sense transcription of ACT1 (Fig. 6I and J), consistent with previous studies (29). Thus, our results demonstrate that Paf1p facilitates GAL10 antisense transcription.…”

Section: Figsupporting

confidence: 81%

“…Likewise, Rad6p promoted sense transcription of ACT1 (Fig. 6A and B), consistent with previous studies (26,29). As a loading control, we showed that the 18S rRNA level was not altered in the ⌬rad6 strain (Fig.…”

Section: Figsupporting

confidence: 79%

“…SET2 was deleted in the wild-type strain (ZDY2; derived from W303a) (27) by the PCR-based gene disruption method to generate SLY7 (28). The RING domain of Bre1p was deleted in YKH045 to generate BUY57 as done previously (29). Multiple Myc epitope tags were added at the original chromosomal loci of SET1 and RAD6 in the wild-type strain (W303a) to generate the PSY4 and PSY2 strains, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, our results demonstrate that Paf1p facilitates GAL10 antisense transcription. Similarly, Paf1p also regulates GAL sense transcription (29).…”

Section: Figmentioning

confidence: 99%

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Regulation of Antisense Transcription by NuA4 Histone Acetyltransferase and Other Chromatin Regulatory Factors

Uprety

Kaja

Ferdoush

et al. 2016

Molecular and Cellular Biology

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NuA4 histone lysine (K) acetyltransferase (KAT) promotes transcriptional initiation of TATA-binding protein (TBP)-associated factor (TAF)-dependent ribosomal protein genes. TAFs have also been recently found to enhance antisense transcription from the 3= end of the GAL10 coding sequence. However, it remains unknown whether, like sense transcription of the ribosomal protein genes, TAF-dependent antisense transcription of GAL10 also requires NuA4 KAT. Here, we show that NuA4 KAT associates with the GAL10 antisense transcription initiation site at the 3= end of the coding sequence. Such association of NuA4 KAT depends on the Reb1p-binding site that recruits Reb1p activator to the GAL10 antisense transcription initiation site. Targeted recruitment of NuA4 KAT to the GAL10 antisense transcription initiation site promotes GAL10 antisense transcription. Like NuA4 KAT, histone H3 K4/36 methyltransferases and histone H2B ubiquitin conjugase facilitate GAL10 antisense transcription, while the Swi/Snf and SAGA chromatin remodeling/modification factors are dispensable for antisense, but not sense, transcription of GAL10. Taken together, our results demonstrate for the first time the roles of NuA4 KAT and other chromatin regulatory factors in controlling antisense transcription, thus illuminating chromatin regulation of antisense transcription. Noncoding RNAs have been implicated in various cellular processes such as X-chromosome inactivation, genomic imprinting, dosage compensation, heterochromatin formation, metabolism, development, and differentiation (1-5). There are several classes of noncoding RNAs, which include microRNAs, small nuclear RNAs, small interfering RNAs, Piwi-interacting RNAs, and natural antisense transcripts (6). About 72% of genes in human and mouse are associated with antisense transcription (7,8). Antisense transcripts arise from the strand opposite to the sense strand and play regulatory functions in interfering with the stability of sense transcripts, and hence gene expression. Therefore, a number of studies have been focused on the use of antisense oligonucleotides in regulation of gene expression and treatment of diseases without permanently altering the genes. In fact, antisense oligonucleotides are in various clinical trials for treatment of diseases such as cancers, hypertension, respiratory illness, and HIV infection (9-13).Despite great potentials of antisense transcripts/transcription in disease pathogenesis and treatment, it is not clearly understood how antisense transcription is initiated. Recently, we have demonstrated that, like in sense transcription, RNA polymerase II is targeted to the 3= end of the GAL10 coding sequence by an activator Reb1p or Reb1p-binding site and general transcription factors (GTFs) such as transcription factor IID (TFIID) (which is composed of TATA-binding protein [TBP] and a set of TBP-associated factors [TAFs]), TFIIB, and Mediator to initiate antisense transcription (14). Further, we have shown that the Gal4p activator and proteasome that facilitate GAL10 s...

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Section: Figsupporting

confidence: 81%

Section: Figsupporting

confidence: 79%

Section: Methodsmentioning

confidence: 99%

“…Thus, our results demonstrate that Paf1p facilitates GAL10 antisense transcription. Similarly, Paf1p also regulates GAL sense transcription (29).…”

Section: Figmentioning

confidence: 99%

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Regulation of Antisense Transcription by NuA4 Histone Acetyltransferase and Other Chromatin Regulatory Factors

Uprety

Kaja

Ferdoush

et al. 2016

Molecular and Cellular Biology

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“…During transcriptional elongation, Spt16 promotes chromatin reassembly in the wake of RNA polymerase II to maintain the fidelity of transcriptional elongation (9)(10)(11). Likewise, histone H2B ubiquitylation is also involved in transcriptional elongation via enhancement of chromatin reassembly in the wake of elongating RNA polymerase II (10,(39)(40)(41). Moreover, histone H2B ubiquitylation (or Rad6/Bre1) and Spt16 interact functionally to promote chromatin reassembly and transcriptional elongation (10).…”

Section: Resultsmentioning

confidence: 99%

Fine-Tuning of FACT by the Ubiquitin Proteasome System in Regulation of Transcriptional Elongation

Sen

Ferdoush

Kaja

et al. 2016

Molecular and Cellular Biology

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FACT (facilitates chromatin transcription), an evolutionarily conserved histone chaperone involved in transcription and other DNA transactions, is upregulated in cancers, and its downregulation is associated with cellular death. However, it is not clearly understood how FACT is fine-tuned for normal cellular functions. Here, we show that the FACT subunit Spt16 is ubiquitylated by San1 (an E3 ubiquitin ligase) and degraded by the 26S proteasome. Enhanced abundance of Spt16 in the absence of San1 impairs transcriptional elongation. Likewise, decreased abundance of Spt16 also reduces transcription. Thus, an optimal level of Spt16 is required for efficient transcriptional elongation, which is maintained by San1 via ubiquitylation and proteasomal degradation. Consistently, San1 associates with the coding sequences of active genes to regulate Spt16's abundance. Further, we found that enhanced abundance of Spt16 in the absence of San1 impairs chromatin reassembly at the coding sequence, similarly to the results seen following inactivation of Spt16. Efficient chromatin reassembly enhances the fidelity of transcriptional elongation. Taken together, our results demonstrate for the first time a fine-tuning of FACT by a ubiquitin proteasome system in promoting chromatin reassembly in the wake of elongating RNA polymerase II and transcriptional elongation, thus revealing novel regulatory mechanisms of gene expression. In eukaryotes, DNA is packaged into nucleosomes to form chromatin. Each nucleosome within chromatin consists of ϳ147 bp of DNA wrapped around a histone octamer containing one histone H3-H4 tetramer and two histone H2A-H2B dimers (1). Thus, chromatin structure plays crucial functions in regulation of DNA transactions such as transcription, replication, and DNA repair (2-4). A variety of factors are involved in altering chromatin structure and, hence, DNA transactions. These factors are generally classified as ATP-independent histone modifying enzymes, ATP-dependent chromatin remodelers, and histone chaperones. Histone modifying enzymes function through addition or removal of specific chemical groups (e.g., acetyl, methyl, ubiquitin, phospho, and SUMO), while ATP-dependent chromatin remodelers alter DNA-histone interactions or the composition of the nucleosome in an ATP-dependent manner. On the other hand, histone chaperones function by binding with nucleosomes or histones to facilitate assembly and/or disassembly of nucleosomes in an ATP-independent fashion. The histone chaperone that was first found to alter chromatin structure during transcription is FACT (facilitates chromatin transcription), which is evolutionarily conserved among eukaryotes (5, 6). In budding yeast (Saccharomyces cerevisiae), FACT is composed of Spt16 (suppressor of Ty) and Pob3 and physically interacts with nucleosomes with the assistance of the HMG (high mobility group) protein Nhp6. Likewise, FACT is also a heterodimer of Spt16 and SSRP1 (structurespecific recognition protein 1) in humans. SSRP1 contains HMG domain, while HMG domain is p...

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Biochemical strategies of E3 ubiquitin ligases target viruses in critical diseases

Dubey

Jagtap

Kumar

et al. 2021

J of Cellular Biochemistry

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Viruses are known to cause various diseases in human and also infect other species such as animal plants, fungi, and bacteria. Replication of viruses depends upon their interaction with hosts. Human cells are prone to such unwanted viral infections. Disintegration and reconstitution require host machinery and various macromolecules like DNA, RNA, and proteins are invaded by viral particles. E3 ubiquitin ligases are known for their specific function, that is, recognition of their respective substrates for intracellular degradation. Still, we do not understand how ubiquitin proteasome system-based enzymes E3 ubiquitin ligases do their

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Functional Analysis of Bre1p, an E3 Ligase for Histone H2B Ubiquitylation, in Regulation of RNA Polymerase II Association with Active Genes and Transcription in Vivo

Cited by 19 publications

References 57 publications

Regulation of Antisense Transcription by NuA4 Histone Acetyltransferase and Other Chromatin Regulatory Factors

Regulation of Antisense Transcription by NuA4 Histone Acetyltransferase and Other Chromatin Regulatory Factors

Fine-Tuning of FACT by the Ubiquitin Proteasome System in Regulation of Transcriptional Elongation

Biochemical strategies of E3 ubiquitin ligases target viruses in critical diseases

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