English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

RNF40 regulates gene expression in an epigenetic context-dependent manner.

MPS-Authors
/persons/resource/persons15488

Mansouri,  A.
Research Group of Molecular Cell Differentiation, MPI for biophysical chemistry, Max Planck Society;

Locator
There are no locators available
Fulltext (public)

2418142.pdf
(Publisher version), 7MB

Supplementary Material (public)

2418142_Suppl_1.docx
(Supplementary material), 10MB

2418142_Suppl_2.xlsx
(Supplementary material), 71KB

2418142_Suppl_3.xls
(Supplementary material), 6MB

2418142_Suppl_4.xlsx
(Supplementary material), 19KB

2418142_Suppl_5.xlsx
(Supplementary material), 18KB

2418142_Suppl_6.xlsx
(Supplementary material), 18KB

Citation

Xie, W., Nagarajan, S., Baumgart, S. J., Kosinsky, R. L., Najafova, Z., Kari, V., et al. (2017). RNF40 regulates gene expression in an epigenetic context-dependent manner. Genome Biology, 18: 32. doi:10.1186/s13059-017-1159-5.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002C-E69B-2
Abstract
Background Monoubiquitination of H2B (H2Bub1) is a largely enigmatic histone modification that has been linked to transcriptional elongation. Because of this association, it has been commonly assumed that H2Bub1 is an exclusively positively acting histone modification and that increased H2Bub1 occupancy correlates with increased gene expression. In contrast, depletion of the H2B ubiquitin ligases RNF20 or RNF40 alters the expression of only a subset of genes. Results Using conditional Rnf40 knockout mouse embryo fibroblasts, we show that genes occupied by low to moderate amounts of H2Bub1 are selectively regulated in response to Rnf40 deletion, whereas genes marked by high levels of H2Bub1 are mostly unaffected by Rnf40 loss. Furthermore, we find that decreased expression of RNF40-dependent genes is highly associated with widespread narrowing of H3K4me3 peaks. H2Bub1 promotes the broadening of H3K4me3 to increase transcriptional elongation, which together lead to increased tissue-specific gene transcription. Notably, genes upregulated following Rnf40 deletion, including Foxl2, are enriched for H3K27me3, which is decreased following Rnf40 deletion due to decreased expression of the Ezh2 gene. As a consequence, increased expression of some RNF40-“suppressed” genes is associated with enhancer activation via FOXL2. Conclusion Together these findings reveal the complexity and context-dependency whereby one histone modification can have divergent effects on gene transcription. Furthermore, we show that these effects are dependent upon the activity of other epigenetic regulatory proteins and histone modifications.