title: A Bre1-associated protein, large 1 (Lge1), promotes H2B ubiquitylation during the early stages of transcription elongation.
abstract: Transcription activation has been proposed to require both ubiquitylation and deubiquitylation of histone H2B. Here, we show that Lge1 (Large 1) is found in a complex containing Rad6.Bre1 and that it controls the recruitment of Bre1, a ubiquitin ligase, and Ubp8, a deubiquitylase, to promote ubiquitylation during the early steps in elongation. Chromatin immunoprecipitation experiments showed that Lge1 associates with promoter and coding regions of actively transcribed genes in a transcription-dependent manner. Disruption of Lge1 abolished ubiquitylation of histone H2B on lysine 123 and H3 methylation on lysines 4 and 79 and resulted in significant sensitivity to 6-azauracil and mycophenolic acid. In particular, in Lge1-deficient cells, Bre1 recruitment was attenuated, whereas recruitment of Ubp8 was facilitated. These alterations were coincident with changes in the interaction between Bre1.Ubp8 and RNA polymerase II phosphorylated at serine 5 of the C-terminal domain. We propose that Lge1 has a novel function in disrupting the balance between the recruitment of Bre1 and Ubp8, thus promoting transcription elongation.
authors.affiliation: Division of Molecular and Life Science, College of Science and Technology, Hanyang University, 1271 Sa 3-dong, Sangnok-gu, Ansan, Gyeonggi-do 426-791, Republic of Korea.
authors.forename: Young-Ha
authors.initials: YH
authors.lastname: Song
authors.forename: Seong Hoon
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D010641:Phenotype; D010766:Phosphorylation / Q000502:physiology; D012319:RNA Polymerase II / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology
chemical_list: C472168:Bre1 protein, S cerevisiae; D002843:Chromatin; D006657:Histones; C497163:Lge1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D012694:Serine; D012319:RNA Polymerase II; D010450:Endopeptidases; C503322:UBP8 protein, S cerevisiae