STARRPeaker: uniform processing and accurate identification of STARR-seq active regions

Lee, Dong‐Hoon; Shi, Manman; Moran, Jennifer R.; Wall, Martha; Zhang, Jing; Liu, Jason; Fitzgerald, Dominic; Kyono, Yasuhiro; Ma, Lijia; White, Kevin P.; Gerstein, Mark

doi:10.1186/s13059-020-02194-x

Cited by 41 publications

(34 citation statements)

References 60 publications

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“…The reads of the two replicates from each sample were sorted and merged and reads falling into regions from the ENCODE blacklist of the mouse reference genome were removed. STARRPeaker (version 1.0) ( 71 ) was used to identify potential enhancers with default parameters and an adjusted P -value threshold of 0.05. Potential enhancers called from STARR-seq data were associated with expressed TE-associated DHSs by overlap using BEDTools.…”

Section: Methodsmentioning

confidence: 99%

Endogenous retroviruses co-opted as divergently transcribed regulatory elements shape the regulatory landscape of embryonic stem cells

Bakoulis

Krautz

Alcaraz

et al. 2022

Nucleic Acids Research

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Transposable elements are an abundant source of transcription factor binding sites, and favorable genomic integration may lead to their recruitment by the host genome for gene regulatory functions. However, it is unclear how frequent co-option of transposable elements as regulatory elements is, to which regulatory programs they contribute and how they compare to regulatory elements devoid of transposable elements. Here, we report a transcription initiation-centric, in-depth characterization of the transposon-derived regulatory landscape of mouse embryonic stem cells. We demonstrate that a substantial number of transposable element insertions, in particular endogenous retroviral elements, are associated with open chromatin regions that are divergently transcribed into unstable RNAs in a cell-type specific manner, and that these elements contribute to a sizable proportion of active enhancers and gene promoters. We further show that transposon subfamilies contribute differently and distinctly to the pluripotency regulatory program through their repertoires of transcription factor binding site sequences, shedding light on the formation of regulatory programs and the origins of regulatory elements.

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Section: Methodsmentioning

confidence: 99%

Endogenous retroviruses co-opted as divergently transcribed regulatory elements shape the regulatory landscape of embryonic stem cells

Bakoulis

Krautz

Alcaraz

et al. 2022

Nucleic Acids Research

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“…This method allows for the simultaneous screening of the entire genome for enhancer activity [ 95 , 102 , 106 ]. There are a number of available methods for analysis of STARR-seq data and identification of enhancer peaks [ 107 , 108 ]. Drawbacks of STARR-seq are twofold; the first being that many enhancers are “context dependent”, meaning that their position in the genome is important, and the STARR-seq approach removes DNA fragments from their genomic context.…”

Section: Direct Methods For Enhancer Discoverymentioning

confidence: 99%

Filtering the Junk: Assigning Function to the Mosquito Non-Coding Genome

Farley

Eggleston

Riehle

2021

Insects

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The portion of the mosquito genome that does not code for proteins contains regulatory elements that likely underlie variation for important phenotypes including resistance and susceptibility to infection with arboviruses and Apicomplexan parasites. Filtering the non-coding genome to uncover these functional elements is an expanding area of research, though identification of non-coding regulatory elements is challenging due to the lack of an amino acid-like code for the non-coding genome and a lack of sequence conservation across species. This review focuses on three types of non-coding regulatory elements: (1) microRNAs (miRNAs), (2) long non-coding RNAs (lncRNAs), and (3) enhancers, and summarizes current advances in technical and analytical approaches for measurement of each of these elements on a genome-wide scale. The review also summarizes and highlights novel findings following application of these techniques in mosquito-borne disease research. Looking beyond the protein-coding genome is essential for understanding the complexities that underlie differential gene expression in response to arboviral or parasite infection in mosquito disease vectors. A comprehensive understanding of the regulation of gene and protein expression will inform transgenic and other vector control methods rooted in naturally segregating genetic variation.

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“…SRP118092 ( https://trace.ncbi.nlm.nih.gov/Traces/sra/?study=SRP118092 ) [ 49 ]) and processed as described by Wang et al [ 50 ]. By analyzing this dataset, we identified ~ 47,000 promoter-distal genomic regions that are enriched for HiDRA signals which was referred to as “STARR active enhancers.” STARR-seq active regions and read density profiles in K562 cells were collected [ 51 ].…”

Section: Methodsmentioning

confidence: 99%

Integrative epigenomic and high-throughput functional enhancer profiling reveals determinants of enhancer heterogeneity in gastric cancer

Sheng

Ooi

et al. 2021

Genome Med

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Background Enhancers are distal cis-regulatory elements required for cell-specific gene expression and cell fate determination. In cancer, enhancer variation has been proposed as a major cause of inter-patient heterogeneity—however, most predicted enhancer regions remain to be functionally tested. Methods We analyzed 132 epigenomic histone modification profiles of 18 primary gastric cancer (GC) samples, 18 normal gastric tissues, and 28 GC cell lines using Nano-ChIP-seq technology. We applied Capture-based Self-Transcribing Active Regulatory Region sequencing (CapSTARR-seq) to assess functional enhancer activity. An Activity-by-contact (ABC) model was employed to explore the effects of histone acetylation and CapSTARR-seq levels on enhancer-promoter interactions. Results We report a comprehensive catalog of 75,730 recurrent predicted enhancers, the majority of which are GC-associated in vivo (> 50,000) and associated with lower somatic mutation rates inferred by whole-genome sequencing. Applying CapSTARR-seq to the enhancer catalog, we observed significant correlations between CapSTARR-seq functional activity and H3K27ac/H3K4me1 levels. Super-enhancer regions exhibited increased CapSTARR-seq signals compared to regular enhancers, even when decoupled from native chromatin contexture. We show that combining histone modification and CapSTARR-seq functional enhancer data improves the prediction of enhancer-promoter interactions and pinpointing of germline single nucleotide polymorphisms (SNPs), somatic copy number alterations (SCNAs), and trans-acting TFs involved in GC expression. We identified cancer-relevant genes (ING1, ARL4C) whose expression between patients is influenced by enhancer differences in genomic copy number and germline SNPs, and HNF4α as a master trans-acting factor associated with GC enhancer heterogeneity. Conclusions Our results indicate that combining histone modification and functional assay data may provide a more accurate metric to assess enhancer activity than either platform individually, providing insights into the relative contribution of genetic (cis) and regulatory (trans) mechanisms to GC enhancer functional heterogeneity.

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STARRPeaker: uniform processing and accurate identification of STARR-seq active regions

Cited by 41 publications

References 60 publications

Endogenous retroviruses co-opted as divergently transcribed regulatory elements shape the regulatory landscape of embryonic stem cells

Endogenous retroviruses co-opted as divergently transcribed regulatory elements shape the regulatory landscape of embryonic stem cells

Filtering the Junk: Assigning Function to the Mosquito Non-Coding Genome

Integrative epigenomic and high-throughput functional enhancer profiling reveals determinants of enhancer heterogeneity in gastric cancer

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