The C-Terminal Domain of RNA Polymerase II Is Modified by Site-Specific Methylation

Sims, Robert J.; Rojas, Luis Alejandro; Beck, David B.; Bonasio, Roberto; Schüller, Roland; Drury, William J.; Eick, Dirk; Reinberg, Danny

doi:10.1126/science.1202663

Cited by 199 publications

(225 citation statements)

References 16 publications

Supporting

Mentioning

221

Contrasting

Unclassified

Order By: Relevance

“…In addition to transcriptional activation, CARM1 methylates splicing factors (32), modulates recognition of 5′ splicing sites (33), and regulates the coupling of transcription and splicing (34). Furthermore, a recent report showed that RNAPII carboxyl-terminal domain is methylated by CARM1 (35). Mutating the CARM1 methylation site in RNAPII carboxylterminal domain affects snoRNA expression similar to the effect observed in CARM1 −/− mouse embryonic fibroblast cells (35).…”

Section: Paf1c and Carm1 Coordinately Regulate A Common Set Of Erαmentioning

confidence: 83%

Histone H3R17me2a mark recruits human RNA Polymerase-Associated Factor 1 Complex to activate transcription

2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The histone coactivator-associated arginine methyltransferase 1 (CARM1) is a coactivator for a number of transcription factors, including nuclear receptors. Although CARM1 and its asymmetrically deposited dimethylation at histone H3 arginine 17 (H3R17me2a) are associated with transcription activation, the mechanism by which CARM1 activates transcription remains unclear. Using an unbiased biochemical approach, we discovered that the transcription elongation-associated PAF1 complex (PAF1c) directly interacts with H3R17me2a. PAF1c binds to histone H3 tails harboring dimethylation at R17 in CARM1-methylated histone octamers. Knockdown of either PAF1c subunits or CARM1 affected transcription of CARM1-regulated, estrogen-responsive genes. Furthermore, either CARM1 knockdown or CARM1 enzyme-deficient mutant knockin resulted in decreased H3R17me2a accompanied by the reduction of PAF1c occupancy at the proximal promoter estrogen-responsive elements. In contrast, PAF1c knockdown elicited no effects on H3R17me2a but reduced the H3K4me3 level at estrogen-responsive elements. These observations suggest that, apart from PAF1c's established roles in directing histone modifications, PAF1c acts as an arginine methyl histone effector that is recruited to promoters and activates a subset of genes, including targets of estrogen signaling.estrogen receptor-α | histone arginine methylation | PRMT

show abstract

Section: Paf1c and Carm1 Coordinately Regulate A Common Set Of Erαmentioning

confidence: 83%

Histone H3R17me2a mark recruits human RNA Polymerase-Associated Factor 1 Complex to activate transcription

2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…130 In addition to the interaction of SMN with R1810me2s, SMN interacts with senataxin (SETX) (Fig. 3A).…”

Section: Smn and Transcriptional Regulationmentioning

confidence: 99%

SMN - A chaperone for nuclear RNP social occasions?

2016

View full text Add to dashboard Cite

Survival Motor Neuron (SMN) protein localizes to both the nucleus and the cytoplasm. Cytoplasmic SMN is diffusely localized in large oligomeric complexes with core member proteins, called Gemins. Biochemical and cell biological studies have demonstrated that the SMN complex is required for the cytoplasmic assembly and nuclear transport of Sm-class ribonucleoproteins (RNPs). Nuclear SMN accumulates with spliceosomal small nuclear (sn)RNPs in Cajal bodies, sub-domains involved in multiple facets of snRNP maturation. Thus, the SMN complex forms stable associations with both nuclear and cytoplasmic snRNPs, and plays a critical role in their biogenesis. In this review, we focus on potential functions of the nuclear SMN complex, with particular emphasis on its role within the Cajal body.

show abstract

“…These modifications suggest a dual gradient model for increasing Ser2 and decreasing Ser5 phosphorylation across genes that regulate transcription 3,4 . In addition to these serine phosphorylations, arginine methylation at one specific residue of the CTD was shown to lead to misregulation of snRNAs as well as small nucleolar RNAs expression 21 .…”

mentioning

confidence: 99%

Serine-7 but not serine-5 phosphorylation primes RNA polymerase II CTD for P-TEFb recognition

2012

View full text Add to dashboard Cite

Phosphorylation of RnA polymerase II carboxy-terminal domain (CTD) in hepta-repeats YsPTsPs regulates eukaryotic transcription. Whereas ser5 is phosphorylated in the initiation phase, ser2 phosphorylation marks the elongation state. Here we show that the positive transcription elongation factor P-TEFb is a ser5 CTD kinase that is unable to create ser2/ser5 double phosphorylations, while it exhibits fourfold higher activity on a CTD substrate prephosphorylated at ser7 compared with the consensus hepta-repeat or the YsPTsPK variant. mass spectrometry reveals an equal number of phosphorylations to the number of heptarepeats provided, yet the mechanism of phosphorylation is distributive despite the repetitive nature of the substrate. Inhibition of P-TEFb activity is mediated by two regions in Hexim1 that act synergistically on Cdk9 and Cyclin T1. HIV-1 Tat/TAR abrogates Hexim1 inhibition to stimulate transcription of viral genes but does not change the substrate specificity. Together, these results provide insight into the multifaceted pattern of CTD phosphorylation.

show abstract

The C-Terminal Domain of RNA Polymerase II Is Modified by Site-Specific Methylation

Cited by 199 publications

References 16 publications

Histone H3R17me2a mark recruits human RNA Polymerase-Associated Factor 1 Complex to activate transcription

Histone H3R17me2a mark recruits human RNA Polymerase-Associated Factor 1 Complex to activate transcription

SMN - A chaperone for nuclear RNP social occasions?

Serine-7 but not serine-5 phosphorylation primes RNA polymerase II CTD for P-TEFb recognition

Contact Info

Product

Resources

About