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High resolution mapping of enhancer-promoter interactions.

Reeder C, Closser M, Poh HM, Sandhu K, Wichterle H, Gifford D - PLoS ONE (2015)

Bottom Line: We show that these genomic locations align more closely with features of active enhancers measured by ChIP-Seq than the locations identified using the ChIA-PET Tool.We also apply Germ to RNA Polymerase II ChIA-PET data from motor neuron progenitors.Based on the Germ results, we observe that a combination of cell type specific and cell type independent regulatory interactions are utilized by cells to regulate gene expression.

View Article: PubMed Central - PubMed

Affiliation: Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.

ABSTRACT
RNA Polymerase II ChIA-PET data has revealed enhancers that are active in a profiled cell type and the genes that the enhancers regulate through chromatin interactions. The most commonly used computational method for analyzing ChIA-PET data, the ChIA-PET Tool, discovers interaction anchors at a spatial resolution that is insufficient to accurately identify individual enhancers. We introduce Germ, a computational method that estimates the likelihood that any two narrowly defined genomic locations are jointly occupied by RNA Polymerase II. Germ takes a blind deconvolution approach to simultaneously estimate the likelihood of RNA Polymerase II occupation as well as a model of the arrangement of read alignments relative to locations occupied by RNA Polymerase II. Both types of information are utilized to estimate the likelihood that RNA Polymerase II jointly occupies any two genomic locations. We apply Germ to RNA Polymerase II ChIA-PET data from embryonic stem cells to identify the genomic locations that are jointly occupied along with transcription start sites. We show that these genomic locations align more closely with features of active enhancers measured by ChIP-Seq than the locations identified using the ChIA-PET Tool. We also apply Germ to RNA Polymerase II ChIA-PET data from motor neuron progenitors. Based on the Germ results, we observe that a combination of cell type specific and cell type independent regulatory interactions are utilized by cells to regulate gene expression.

No MeSH data available.


Related in: MedlinePlus

Visualization of ChIP-Seq data in regions detected to interact with TSSs.The top row of boxes contains TSS-distal, TSS jointly occupied regions identified by GermTSS. The bottom row of boxes contains the corresponding regions from [27]. The 6 kilobase regions are centered on the estimated eloc or midpoint and are ordered by the significance associated with the interaction. Each column represents data from a ChIP-Seq dataset that is associated with active enhancers.
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pone.0122420.g003: Visualization of ChIP-Seq data in regions detected to interact with TSSs.The top row of boxes contains TSS-distal, TSS jointly occupied regions identified by GermTSS. The bottom row of boxes contains the corresponding regions from [27]. The 6 kilobase regions are centered on the estimated eloc or midpoint and are ordered by the significance associated with the interaction. Each column represents data from a ChIP-Seq dataset that is associated with active enhancers.

Mentions: We applied Germ to PolII ChIA-PET data from ESCs [27] to identify locations that interact with TSSs. By examining ChIP-Seq data for several features of active enhancers at the locations that Germ detects as interacting with TSSs we found that these locations align closely with locations that appear to be active enhancers. We incorporated a set of annotated TSSs from the UCSC knownGene database to profile the occupancy of PolII conditioned on the locations of the annotated TSSs. For each TSS, Germ provided a set of regions that are jointly occupied by PolII along with the TSS. The joint occupation of a region with a TSS by PolII indicates that this region is spatially proximal to the TSS and that PolII is also present at the junction between the region and the TSS. PolII tends to occupy relatively broad regions of the genome, but upon examining the distributions of PolII occupancy that we estimate with Germ, we observed that regions of elevated occupancy generally contain locations with locally maximal likelihood of occupancy. We noted the location within each TSS-interacting region that Germ determines to be the most likely anchor point for the interaction. As shown in Fig 3, the Germ estimated anchor points are informative in that they align closely with maximal locations of enrichment for active enhancer-related ChIP-Seq data.


High resolution mapping of enhancer-promoter interactions.

Reeder C, Closser M, Poh HM, Sandhu K, Wichterle H, Gifford D - PLoS ONE (2015)

Visualization of ChIP-Seq data in regions detected to interact with TSSs.The top row of boxes contains TSS-distal, TSS jointly occupied regions identified by GermTSS. The bottom row of boxes contains the corresponding regions from [27]. The 6 kilobase regions are centered on the estimated eloc or midpoint and are ordered by the significance associated with the interaction. Each column represents data from a ChIP-Seq dataset that is associated with active enhancers.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4430501&req=5

pone.0122420.g003: Visualization of ChIP-Seq data in regions detected to interact with TSSs.The top row of boxes contains TSS-distal, TSS jointly occupied regions identified by GermTSS. The bottom row of boxes contains the corresponding regions from [27]. The 6 kilobase regions are centered on the estimated eloc or midpoint and are ordered by the significance associated with the interaction. Each column represents data from a ChIP-Seq dataset that is associated with active enhancers.
Mentions: We applied Germ to PolII ChIA-PET data from ESCs [27] to identify locations that interact with TSSs. By examining ChIP-Seq data for several features of active enhancers at the locations that Germ detects as interacting with TSSs we found that these locations align closely with locations that appear to be active enhancers. We incorporated a set of annotated TSSs from the UCSC knownGene database to profile the occupancy of PolII conditioned on the locations of the annotated TSSs. For each TSS, Germ provided a set of regions that are jointly occupied by PolII along with the TSS. The joint occupation of a region with a TSS by PolII indicates that this region is spatially proximal to the TSS and that PolII is also present at the junction between the region and the TSS. PolII tends to occupy relatively broad regions of the genome, but upon examining the distributions of PolII occupancy that we estimate with Germ, we observed that regions of elevated occupancy generally contain locations with locally maximal likelihood of occupancy. We noted the location within each TSS-interacting region that Germ determines to be the most likely anchor point for the interaction. As shown in Fig 3, the Germ estimated anchor points are informative in that they align closely with maximal locations of enrichment for active enhancer-related ChIP-Seq data.

Bottom Line: We show that these genomic locations align more closely with features of active enhancers measured by ChIP-Seq than the locations identified using the ChIA-PET Tool.We also apply Germ to RNA Polymerase II ChIA-PET data from motor neuron progenitors.Based on the Germ results, we observe that a combination of cell type specific and cell type independent regulatory interactions are utilized by cells to regulate gene expression.

View Article: PubMed Central - PubMed

Affiliation: Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.

ABSTRACT
RNA Polymerase II ChIA-PET data has revealed enhancers that are active in a profiled cell type and the genes that the enhancers regulate through chromatin interactions. The most commonly used computational method for analyzing ChIA-PET data, the ChIA-PET Tool, discovers interaction anchors at a spatial resolution that is insufficient to accurately identify individual enhancers. We introduce Germ, a computational method that estimates the likelihood that any two narrowly defined genomic locations are jointly occupied by RNA Polymerase II. Germ takes a blind deconvolution approach to simultaneously estimate the likelihood of RNA Polymerase II occupation as well as a model of the arrangement of read alignments relative to locations occupied by RNA Polymerase II. Both types of information are utilized to estimate the likelihood that RNA Polymerase II jointly occupies any two genomic locations. We apply Germ to RNA Polymerase II ChIA-PET data from embryonic stem cells to identify the genomic locations that are jointly occupied along with transcription start sites. We show that these genomic locations align more closely with features of active enhancers measured by ChIP-Seq than the locations identified using the ChIA-PET Tool. We also apply Germ to RNA Polymerase II ChIA-PET data from motor neuron progenitors. Based on the Germ results, we observe that a combination of cell type specific and cell type independent regulatory interactions are utilized by cells to regulate gene expression.

No MeSH data available.


Related in: MedlinePlus