Widespread transcription at neuronal activity-regulated enhancers

By Tae-Kyung Kim, Martin Hemberg, Jesse M. Gray, Allen M. Costa, Daniel M. Bear, Jing Wu, D. Harmin, M. Laptewicz, Kellie Barbara-Haley, S. Kuersten and 6 more. Nature, 2010

1,879 citations recorded by the source corpus.

We used genome-wide sequencing methods to study stimulus-dependent enhancer function in mouse cortical neurons. We identified ∼12,000 neuronal activity-regulated enhancers that are bound by the general transcriptional co-activator CBP in an activity-dependent manner. A function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4. The level of eRNA expression at neuronal enhancers positively correlates with the level of messenger RNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis. These findings reveal that a widespread mechanism of enhancer activation involves RNAPII binding and eRNA synthesis.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/bc7c5b37e8e999891e7f4e5e76e799bf3e8d0f4b

How researchers see this paper

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

In Molecular Biology

Citations in the corpus

Remodeling of the enhancer landscape during macrophage activation is coupled to enhancer transcription (2013, neutral): “Recent studies of nuclear RNAs in neurons (Kim et al., 2010), cancer cells (Hah et al.”
Analysis of nascent RNA identifies a unified architecture of initiation regions at mammalian promoters and enhancers (2014, neutral): “This HMM identified a total of ~120K putative TSSs in each cell line, within the range previously reported (80 to 150 K) 8, 10, 26, 27 .”
Charting histone modifications and the functional organization of mammalian genomes (2011, background): “found that RNAPII interacts with many active enhancers that were identified by the chromatin patterns in these cells and transcribes bidirectional short (”
Enhancer function: new insights into the regulation of tissue-specific gene expression (2011, neutral): “Interestingly, CBP recruits RNAPII at a subset of these enhancers to transcribe a novel class of non-coding RN”
Transcriptional Regulation and its Misregulation in Disease (2013, neutral): “6 eRNAs are generated from active enhancers, thus the number of eRNAs depends on the set of active enhancers in a cell (Kim et al., 2010; Wang et al., 2011).”
Cell Types, Network Homeostasis, and Pathological Compensation from a Biologically Plausible Ion Channel Expression Model. (2015, neutral): “Furthermore, transcriptional changes in ion channel genes occur in response to activity perturbations (Kim et al., 2010) and may underlie homeostatic regulation of network activity (Thoby-Brisson and Simmers 2000).”
Long Noncoding RNAs: Past, Present, and Future (2013, neutral): “The discovery of eRNAs (Kim et al. 2010) raises the possibility that similar transcription-based mechanisms may operate at mammalian enhancers, although at present, the biological function of these RNAs is under debate.”
The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression (2012, positive): “studies have demonstrated either positive (Kim et al. 2010; Ørom et al. 2010) or negative (Brockdorff et al.”
Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis. (2012, neutral): “Additional recently identified cis-acting RNAs activate the expression of neigh- boring genes (Kim et al. 2010; Ørom et al. 2010; Wang et al. 2011).”
Architectural protein subclasses shape 3D organization of genomes during lineage commitment. (2013, neutral): “…displaying H3K4me3 Cell 153, 1–15, June 6, 2013 ª2013 Elsevier Inc. 9 (legend on next page) 10 Cell 153, 1–15, June 6, 2013 ª2013 Elsevier Inc. signal and RNA Pol II occupancy, suggesting that enhancers marked by H3K4me3 might have active transcription of eRNAs (Kim et al., 2010) (Figure 7A).”
PEDLA: predicting enhancers with a deep learning-based algorithmic framework (2016, positive): “Next, we strictly used the highly reliable H3K27ac peaks, which met the following criteria as described previously (10): (1) H3K27ac peaks that were located within 1 kb of all annotated transcription start sites (TSSs) of protein-coding genes annotated by GENCODE (V15) (60) were removed.”