Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells

By A. Marson, S. Levine, Megan F. Cole, G. Frampton, T. Brambrink, Sarah E. Johnstone, M. Guenther, W. K. Johnston, Marius Wernig, J. Newman and 10 more. Cell, 2008

1,426 citations recorded by the source corpus.

SUMMARY MicroRNAs (miRNAs) are crucial for normal embryonic stem (ES) cell self-renewal and cellular differentiation, but how miRNA gene expression is controlled by the key transcriptional regulators of ES cells has not been established. We describe here a new map of the transcriptional regulatory circuitry of ES cells that incorporates both protein-coding and miRNA genes, and which is based on high-resolution ChIP-seq data, systematic identification of miRNA promoters, and quantitative sequencing of short transcripts in multiple cell types. We find that the key ES cell transcription factors are associated with promoters for most miRNAs that are preferentially expressed in ES cells and with promoters for a set of silent miRNA genes. This silent set of miRNA genes is co-occupied by Polycomb Group proteins in ES cells and expressed in a tissue-specific fashion in differentiated cells. These data reveal how key ES cell transcription factors promote the miRNA expression program that contributes to normal self-renewal and cellular differentiation, and integrate miRNAs and their targets into an expanded model of the regulatory circuitry controlling ES cell identity.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a44aa96ff16b00574662b7cbc169da7514aee254

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

In Molecular Biology

Citations in the corpus

miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis (2010, background): “Recently, others have identified candidate transcriptional start sites (TSSs) and promoters of the great majority of human and mouse miRNA gene”
MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. (2009, neutral): “In addition to protein-coding genes, a group of noncoding microRNA (miRNA) genes are connected to the transcriptional regulatory circuitry of ESCs (Marson et al., 2008).”
Metazoan MicroRNAs (2018, background): “All other canonical and nearly all other noncanonical miRNA loci are also under Pol II transcriptional control, which is indistinguishable from that of protein-coding genes (O’Donnell et al., 2005; Marson et al., 2008; Ozsolak et al., 2008).”
Systems biology of stem cell fate and cellular reprogramming (2009, neutral): “Furthermore, recent reports have also connected miRNA”
Embryonic Stem Cell-Derived Exosomes Promote Endogenous Repair Mechanisms and Enhance Cardiac Function Following Myocardial Infarction (2015, background): “in ESCs and forms 70% of the known miRNAs produced by ESCs.(27,28) Furthermore, members of the miR-290 family are Figure 5.”
MicroRNAs: key regulators of stem cells (2009, background): “Furthermore, a recent genome-wide chromatin immunoprecipitation coupled with DNA sequencing (ChIP-seq) study has shown, at high resolution, that key ES cell-specific transcription factors bind to promoters of ES cell-specific miRNAs and directly promote their expressio”
Histone H3K27ac separates active from poised enhancers and predicts developmental state (2010, methodology): “We generated data sets for p300 and H3K27ac and adapted datasets for Oct4, Sox2, Klf4, p300, and Nanog from previous work (18, 19) and found that a significant amount of the putative ES cell enhancers identified here were enriched for the factors tested (Fig.”
Mediator and Cohesin Connect Gene Expression and Chromatin Architecture (2010, neutral): “Chromatin immunoprecipitations (ChIPs) were performed and analyzed as previously described 49 .”
Master Transcription Factors Determine Cell-Type-Specific Responses to TGF-β Signaling (2011, positive): “The association of genes bound by each transcription factor with genes affected by TGF-b signaling (significance of transcription factor occupancy at genes affected by TGF-b signaling, x axis) was calculated for genes bound by Oct4, Sox2, Nanog, Smad3, and Zfx (y axis).”
STAT3 activation of miR-21 and miR-181b-1, via PTEN and CYLD, are part of the epigenetic switch linking inflammation to cancer (2010, methodology): “To annotate the TSS for the microRNAs, we incorporated the findings from Ozsolak et al. (2008) and Marson et al. (2008) and mapped the genome coordinates to the hg18 version of the human genome by using liftOver program from UCSC.”
Non-coding RNAs as regulators of embryogenesis (2011, background): “Whereas most promoters of ES cell-specific miRNAs are bound and induced by OCT4, SOX2, Nanog and TCF3 (Ref”