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H2B ubiquitylation is part of chromatin architecture that marks exon-intron structure in budding yeast

Grace S Shieh1, Chin-Hua Pan2, Jia-Hong Wu1, Yun-Ju Sun1, Chia-Chang Wang1, Wei-Chun Hsiao2, Chia-Yeh Lin2, Luh Tung3, Tien-Hsien Chang3, Alastair B Fleming5, Cory Hillyer7, Yi-Chen Lo4, Shelley L Berger6, Mary Ann Osley7* and Cheng-Fu Kao2*

Author Affiliations

1 Institute of Statistical Sciences, Academia Sinica, Academia Road, Nankang, Taipei 115, Taiwan

2 Institute of Cellular and Organismic Biology, Academia Sinica, Academia Road, Nankang, Taipei 115, Taiwan

3 Genomic Research Center, Academia Sinica, Academia Road, Nankang, Taipei 115, Taiwan

4 Institute of Food Science and Technology, National Taiwan University, Daan, Taipei 106, Taiwan

5 Microbiology, Moyne Institute of Preventive Medicine, The University of Dublin, Trinity College, College Green, Dublin2, Dublin, Ireland

6 Departments of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA

7 Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA

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BMC Genomics 2011, 12:627  doi:10.1186/1471-2164-12-627

Published: 22 December 2011



The packaging of DNA into chromatin regulates transcription from initiation through 3' end processing. One aspect of transcription in which chromatin plays a poorly understood role is the co-transcriptional splicing of pre-mRNA.


Here we provide evidence that H2B monoubiquitylation (H2BK123ub1) marks introns in Saccharomyces cerevisiae. A genome-wide map of H2BK123ub1 in this organism reveals that this modification is enriched in coding regions and that its levels peak at the transcribed regions of two characteristic subgroups of genes. First, long genes are more likely to have higher levels of H2BK123ub1, correlating with the postulated role of this modification in preventing cryptic transcription initiation in ORFs. Second, genes that are highly transcribed also have high levels of H2BK123ub1, including the ribosomal protein genes, which comprise the majority of intron-containing genes in yeast. H2BK123ub1 is also a feature of introns in the yeast genome, and the disruption of this modification alters the intragenic distribution of H3 trimethylation on lysine 36 (H3K36me3), which functionally correlates with alternative RNA splicing in humans. In addition, the deletion of genes encoding the U2 snRNP subunits, Lea1 or Msl1, in combination with an htb-K123R mutation, leads to synthetic lethality.


These data suggest that H2BK123ub1 facilitates cross talk between chromatin and pre-mRNA splicing by modulating the distribution of intronic and exonic histone modifications.