ChIP-seq accurately predicts tissue-specific activity of enhancers

By Axel Visel, M. Blow, Zirong Li, Tao Zhang, J. Akiyama, Amy Holt, I. Plajzer-Frick, Malak Shoukry, Crystal Wright, Feng Chen and 4 more. Nature, 2009

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A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant-acting transcriptional enhancers are particularly challenging to uncover because they are scattered among the vast non-coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue. We tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases demonstrated reproducible enhancer activity in the tissues that were predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities, and suggest that such data sets will be useful to study the role of tissue-specific enhancers in human biology and disease on a genome-wide scale.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a0c989cd0d00dbe6c949e0d87111ce27dda94316

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Citations in the corpus

Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes (2013, positive): “The number of enhancers that are active in any one cell type has been estimated to be in the tens of thousands and enhancer activity is largely cell type-specific (Bernstein et al., 2012; Heintzman et al., 2009; Shen et al., 2012; Visel et al., 2009; Yip et al., 2012).”
Integrative annotation of chromatin elements from ENCODE data (2012, neutral): “The ChromHMM and Segway Enh states show the strongest enrichment for the transcriptional coactivator p300, often found at enhancers (25) (Supplementary Figure S18).”
Super-enhancers in the control of cell identity and disease. (2013, neutral): “The set of enhancers that control any one cell’s gene expression program is probably best defined in murine embryonic stem cells (ESCs).”
Pioneer transcription factors: establishing competence for gene expression. (2011, background): “The location of histone-modifying enzymes, such as the lysine acetyltransferase p300 at enhancers (Visel et al. 2009), and histone modifications, such as histone H3K4 methylation at active enhancers and promoters (Heintzman et al.”
GREAT improves functional interpretation of cis-regulatory regions (2010, methodology): “P300 binding in the developing mouse limbs Second, we analyzed a recent ChIP-seq data set comprising 2,105 regions of the mouse genome bound by the general enhancer-associated protein p300 in embryonic limb tissu”
A unique chromatin signature uncovers early developmental enhancers in humans (2010, methodology): “Specificity of our reporter assays was validated by assaying an extensive set of negative controls (Supplementary Table 4): (1) five class I elements; (2) four nonconserved genomic regions in proximity of four of the tested class II elements; (3) four human adult-tissue-specific enhancers that shoul”
High Resolution Genome Wide Binding Event Finding and Motif Discovery Reveals Transcription Factor Spatial Binding Constraints (2012, background): “…out of 123) of these regions are bound by p300, a histone acetyltransferase and transcriptional coactivator that predicts tissue-specific enhancers [30]; the majority of these regions are also marked by H3K27ac, a histone modification associated with active enhancers [29], suggesting that they may…”
Needles in stacks of needles: finding disease-causal variants in a wealth of genomic data (2011, neutral): “In addition, progress is being made in identifying long-range regulatory elements (for example, REFS 90,104 ) and matching them to their target genes through techniques such as chromosome conformation capture 105 .”
Transcriptional enhancers: from properties to genome-wide predictions (2014, methodology): “In fact, this activity — which is independent of the sequence context of the enhancer and can be assessed in heterologous reporter systems — has been the defining property of enhancers 1 and is used as the ‘gold standard’ to evaluate enhancer predictions 50–52 ,”
DNaseI sensitivity QTLs are a major determinant of human expression variation (2012, neutral): “Finally, the presence of the enhancer mark P300 (from ENCODE ChIP-seq dat”
BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis (2015, methodology): “HbF enrichment score was determined by calculating (1) the ratio of normalized reads in the HbF-high compared to reads in the HbF-low pools; (2) log2 transformation; and (3) median of biological replicates.”
The Human Transcription Factors. (2018, neutral): “Some coactivators and corepressors appear to bemorewidely used than others. p300 is often used as a marker of enhancers (Visel et al., 2009), associating with dozens of TFs (Frietze and Farnham, 2011).”
Disruptions of Topological Chromatin Domains Cause Pathogenic Rewiring of Gene-Enhancer Interactions (2015, background): “We obtained heterozygous and homozygous ESC clones carrying a 1.06-Mb CRISPR-induced inversion with breakpoints at comparable positions in the mouse locus (Figure 3C).”