Bre1, an E3 Ubiquitin Ligase Required for Recruitment and Substrate Selection of Rad6 at a Promoter

Department of Biochemistry, Saint Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104, USA.
Molecular Cell (Impact Factor: 14.02). 02/2003; 11(1):267-74. DOI: 10.1016/S1097-2765(02)00802-X
Source: PubMed

ABSTRACT Ubiquitination of histone H2B catalyzed by Rad6 is required for methylation of histone H3 by COMPASS. We identified Bre1 as the probable E3 for Rad6's role in transcription. Bre1 contains a C3HC4 (RING) finger and is present with Rad6 in a complex. The RING finger of Bre1 is required for ubiquitination of histone H2B, methylation of lysine 4 and 79 of H3 and for telomeric silencing. Chromatin immunoprecipitation experiments indicated that both Rad6 and Bre1 are recruited to a promoter. Bre1 is essential for this recruitment of Rad6 and is dedicated to the transcriptional pathway of Rad6. These results suggest that Bre1 is the likely E3 enzyme that directs Rad6 to modify chromatin and ultimately to affect gene expression.

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Available from: Jim Dover, Sep 27, 2015
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    • "Euchromatin in the yeast Saccharomyces cerevisiae is characterized by Dot1-mediated H3K79 trimethylation (H3K79me3) (Briggs et al. 2002; van Leeuwen et al. 2002; Henry et al. 2003; Wood et al. 2003; Kao et al. 2004; Xiao et al. 2005; Pavri et al. 2006; Shilatifard 2006). H3K79me3, a mark closely associated with active transcription , is typically present in the coding regions of genes but absent from intergenic regions as well as subtelomeric heterochromatin (Ng et al. 2003; Pokholok et al. 2005), both of which are transcriptionally silent. "
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    Genes & Development 02/2015; 29(4):350-5. DOI:10.1101/gad.256255.114 · 10.80 Impact Factor
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    • "It contains a highly conserved catalytic UBC domain of approximately 150 amino acids in length with an active-site cysteine for linking Ub. The E3 enzyme working together with Rad6 in catalyzing H2Bub1 formation in budding yeast is Bre1 (Brefeldin-A sensitivity protein 1), which contains a C3HC4-type RING finger domain typical for all E3s (Hwang et al., 2003; Wood et al., 2003). The depletion of either Rad6 or Bre1 eliminates genome-wide H2Bub1 and causes yeast cell growth defects (Robzyk et al., 2000; Hwang et al., 2003; Wood et al., 2003). "
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    Frontiers in Plant Science 03/2014; 5:83. DOI:10.3389/fpls.2014.00083 · 3.95 Impact Factor
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    • "The K-rich domain of Dot1 appears to interact with the mono-ubiquitinated H2B K123 [102], and the acidic domain of Dot1 interacts with the H4RHR [100,101] (Figure 3). Histone H2B K123 mono-methylation is catalyzed by the ubiquitin ligase Bre1 along with the ubiquitin conjugase Rad6 [103,104]. Paf1C, a 5-subunit complex involved in transcription elongation, is required for mono-ubiquitination of H2B K123 by Bre1 and Rad6 [105–107]. It appears that a small region (residues 62–152) of Rtf1, a subunit of Paf1C, can substitute for the complete Paf1C in facilitating global H2B K123 mono-ubiquitination and di- and tri-methylation of H3 K79 in yeast [108]. "
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