Ubiquitylation of the COMPASS component Swd2 links H2B ubiquitylation to H3K4 trimethylation

Abstract

Mono-ubiquitylation of histone H2B correlates with transcriptional activation and is required for di- and trimethylation at Lys 4 on the histone H3 tail (H3K4) by the SET1/COMPASS methyltransferase complex through a poorly characterized trans-tail pathway. Here we show that mono-ubiquitylation of histone H2B promotes ubiquitylation at Lys 68 and Lys 69 of Swd2, the essential component of SET1/COMPASS in Saccharomyces cerevisiae. We found that Rad6/Bre1 ubiquitylation enzymes responsible for H2B ubiquitylation also participate directly in Swd2 modification. Preventing Swd2 or H2B ubiquitylation did not affect Set1 stability, interaction of Swd2 with Set1 or the ability of Swd2 to interact with chromatin. However, we found that mutation of Lys 68 and Lys 69 of Swd2 markedly reduced trimethylation, and to a lesser extent dimethylation, of H3K4 at the 5'-end of transcribing genes without affecting monomethylation. This effect results from the ability of Swd2 ubiquitylation to control recruitment of Spp1, a COMPASS subunit necessary for trimethylation. Our results further indicate that Swd2 is a major H3-binding component of COMPASS. Swd2 thus represents a key factor that mediates crosstalk between H2B ubiquitylation and H3K4 trimethylation on chromatin.

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

“…Thus, the ⌬bre1 strain used in our study does not appear to contain a hidden mutation. Similar to our results, a recent study in S. cerevisiae also demonstrated that association of RNA polymerase II with GAL10 and PMA1 was not decreased in the ⌬bre1 strain (14).…”

“…Thus, the repressive role of Bre1p appears to be restricted to transcription, but not DNA repair or replication. Likewise, a recent study in S. cerevisiae also showed that the association of RNA polymerase II with GAL10 and PMA1 was not decreased in the null mutant of BRE1 in comparison to the wild-type equivalent (14). On the other hand, the association of RNA polymerase II with these genes was significantly impaired in the H2B-K123R point mutant strain (14).…”

“…Histone H2B ubiquitylation has been implicated in transcriptional elongation (8 -13), and thus, the association of RNA polymerase II with the coding sequence of the active gene is significantly decreased in the absence of histone H2B ubiquitylation (8 -12). A complex of three proteins, Rad6p (E2 ubiquitin conjugase), Bre1p (E3 ubiquitin ligase) and Lge1p, is essential for histone H2B Lys-123 ubiquitylation in Saccharomyces cerevisiae (2,4,5,(13)(14)(15)(16)(17)(18)(19). This complex shows a very specific subset of synthetically fitness or lethal defect interactions with the SWR1 chromatin remodeling complex (9) and Sin3p/Rpd3p histone deacetylase (18).…”

Yeast Swd2 Is Essential Because of Antagonism between Set1 Histone Methyltransferase Complex and APT (Associated with Pta1) Termination Factor

“…Although this result does not distinguish whether Swd2 and Set1 bind in sequence or together, it argues H3K4 monomethylation is not sufficient and that Set1 is important for Swd2 cross-linking. Dehé et al (59) did not observe a similar loss of Set1 binding in the rad6⌬ strain, but Vitaliano-Prunier et al (60) reported that deletion of the Rad6 partner Bre1 partially reduced Swd2 recruitment without disrupting the association between Swd2 and Set1.…”

Increase in Tomato Locule Number Is Controlled by Two Single-Nucleotide Polymorphisms Located NearWUSCHEL

“…The WD40 repeat protein was also a likely candidate because these proteins are linked to several important functions in eukaryotes (Smith et al, 1999), such as cell division (Feldman et al, 1997) and chromatin remodeling (Vitaliano-Prunier et al, 2008).…”