Transcriptomics,Genomics

Dataset Information

358

The RNA Pol II Elongation Factor Ell3 Marks Enhancers in ES Cells and Primes Future Gene Activation


ABSTRACT: Enhancers play a central role in precisely regulating the spatiotemporal expression of developmentally regulated genes. The molecular mechanisms and factors required for controlling the inactive or poised enhancers and their function in future gene activation remain elusive. Here, we have identified that Ell3, a member of the Ell (Eleven-nineteen Lysine-rich Leukemia gene) family of RNA Pol II elongation factors, predominately occupies active and inactive enhancers of many developmentally regulated genes in mouse embryonic stem cells. Ell3 localizes to active enhancers of key stem cell renewal genes, but is not required for maintaining the undifferentiated state. Instead, Ell3 binding to inactive or poised enhancers is essential for marking them for stem cell specification through regulating the activation of key lineage-specific genes throughout differentiation. Ell3’s association with enhancers is required for setting up proper Pol II occupancy at the proximal promoter regions of neighboring genes. This functional interaction between Ell3 and proximal promoter Pol II is dependent on cohesin. The depletion of cohesin subunits removes Ell3 from the enhancers and results in reduction in the levels of promoter proximally paused Pol II. Our study demonstrates that Ell3 is required for stem cell fate specification through regulating Pol II pausing on key developmental genes in the undifferentiated state and for their proper expression during differentiation. ChIP-seq of Ell3 in mES cells. ChIP-seq of Pol II in mES cells after Ell3 shRNA and non-targeting shRNA. RNA-seq of mES cells after Ell3 shRNA and non-targeting shRNA. RNA-seq of mouse embryoid bodies at day five after non-targeting shRNA.

ORGANISM(S): Mus musculus  

SUBMITTER: Ali Shilatifard   Alexander S Garruss  Chengqi Lin  Alexander (Garrett) Garruss 

PROVIDER: E-GEOD-38148 | ArrayExpress | 2012-12-30

SECONDARY ACCESSION(S): SRP013333GSE38148PRJNA167281

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

The RNA Pol II elongation factor Ell3 marks enhancers in ES cells and primes future gene activation.

Lin Chengqi C   Garruss Alexander S AS   Luo Zhuojuan Z   Guo Fengli F   Shilatifard Ali A  

Cell 20121227 1-2


Enhancers play a central role in precisely regulating the expression of developmentally regulated genes. However, the machineries required for enhancer-promoter communication have remained largely unknown. We have found that Ell3, a member of the Ell (eleven-nineteen lysine-rich leukemia gene) family of RNA Pol II elongation factors, occupies enhancers in embryonic stem cells. Ell3's association with enhancers is required for setting up proper Pol II occupancy at the promoter-proximal regions of  ...[more]

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