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Corrigendum: Corrigendum: A systematic comparison reveals substantial differences in chromosomal versus episomal encoding of enhancer activity
- Fumitaka Inoue,
- Martin Kircher,
- Beth Martin,
- Gregory M. Cooper,
- Daniela M. Witten,
- Michael T. McManus,
- Nadav Ahituv,
- and Jay Shendure
Genome Res. May 2018 28: 766.3; doi:10.1101/gr.237321.118
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Review: A systematic guide for identifying transcription factors that directly regulate the expression of a gene of interest
- Andrew D. Bates,
- Dawid Grzela,
- Maciej Studzian,
- Louise Brennan,
- Moli Williams,
- Conor Fawcett,
- Beth Hammond,
- Manreen Grewal,
- Marcin Ratajewski,
- Lukasz Pulaski,
- and Urszula L. McClurg
Genome Res. March 2026 36: 433-459; Published in Advance February 17, 2026, doi:10.1101/gr.281154.125
...).Beyond biological relevance, it is also important to distinguish between methods that study the steady state of the cell versus those that introduce experimental perturbations for comparative analysis. Some techniques rely on genetic modifications to reveal functional differences. Gain-of-function approaches...
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Research: Systematic interrogation of human promoters
- Shira Weingarten-Gabbay,
- Ronit Nir,
- Shai Lubliner,
- Eilon Sharon,
- Yael Kalma,
- Adina Weinberger,
- and Eran Segal
Genome Res. February 2019 29: 171-183; Published in Advance January 8, 2019, doi:10.1101/gr.236075.118
....3% unidirectional versus 27.5% and 20.7% bidirectional expression from promoter and enhancer regions, respectively (Fig. 2D,E). The general unidirectional activity is also demonstrated by negative correlation between expression measurements in the plus and minus strands for promoters (R = −0.27, P < 0...
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Method: ATAC-STARR-seq reveals transcription factor–bound activators and silencers within chromatin-accessible regions of the human genome
- Tyler J. Hansen and
- Emily Hodges
Genome Res. August 2022 32: 1529-1541; Published in Advance July 20, 2022, doi:10.1101/gr.276766.122
.... Therefore, chromatin accessibility is a vital regulator of enhancer function, and this is evidenced by the observation that ∼94% of all ENCODE TF ChIP-seq peaks fall within accessible chromatin (Klemm et al. 2019). In any given cell type, only a small fraction (∼2%) of the is accessible to TF binding...
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Research: A massively parallel reporter assay reveals context-dependent activity of homeodomain binding sites in vivo
- Andrew E.O. Hughes,
- Connie A. Myers,
- and Joseph C. Corbo
Genome Res. October 2018 28: 1520-1531; Published in Advance August 29, 2018, doi:10.1101/gr.231886.117
..., at least in part, technical in nature. Accordingly, we restricted subsequent analyses to data generated on pCrx, which appears to have a broader dynamic range.Dimeric CRX binding sites encode stronger enhancers than monomeric CRX binding sitesAs discussed above, homeodomain TFs bind DNA as both monomers...
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Research: Pathogenic variants in CRX have distinct cis-regulatory effects on enhancers and silencers in photoreceptors
- James L. Shepherdson,
- Ryan Z. Friedman,
- Yiqiao Zheng,
- Chi Sun,
- Inez Y. Oh,
- David M. Granas,
- Barak A. Cohen,
- Shiming Chen,
- and Michael A. White
Genome Res. February 2024 34: 243-255; Published in Advance February 14, 2024, doi:10.1101/gr.278133.123
...-bound loci are partially predictive of episomal MPRA activity, and distal elements whose accessibility increases later in retinal development are enriched for CREs with silencer activity. We identified a set of potentially pleiotropic regulatory elements that convert from silencers to enhancers in retinas...
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Perspective: Challenges and considerations for reproducibility of STARR-seq assays
- Maitreya Das,
- Ayaan Hossain,
- Deepro Banerjee,
- Craig Alan Praul,
- and Santhosh Girirajan
Genome Res. April 2023 33: 479-495; Published in Advance May 2, 2023, doi:10.1101/gr.277204.122
...-seq), like other episomal massively parallel reporter assays (MPRAs) (Melnikov et al. 2012; Patwardhan et al. 2012), directly quantifies enhancer activity by relying on transcription factors within a host cell system, thereby removing any chromatin-associated biases (Arnold et al. 2013). STARR-seq takes...
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Resource: MPRAbase a Massively Parallel Reporter Assay database
- Jingjing Zhao,
- Fotis A Baltoumas,
- Maxwell A Konnaris,
- Ioannis Mouratidis,
- Zhe Liu,
- Jasmine Sims,
- Vikram Agarwal,
- Georgios A Pavlopoulos,
- Ilias Georgakopoulos-Soares,
- and Nadav Ahituv
Genome Res. April 22, 2025 gr.280387.124; Published in Advance April 22, 2025, doi:10.1101/gr.280387.124
...reveals substantial differences in chromosomal versus episomal encoding of enhancer activity. Genome Res 27: 38–52. Johnson GD, Barrera A, McDowell IC, D’Ippolito AM, Majoros WH, Vockley CM, Wang X, Allen AS, Reddy TE. 2018. Human -wide measurement of drug-responsive regulatory activity. Nat Commun 9...
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Method: Sequence-based correction of barcode bias in massively parallel reporter assays
- Dongwon Lee,
- Ashish Kapoor,
- Changhee Lee,
- Michael Mudgett,
- Michael A. Beer,
- and Aravinda Chakravarti
Genome Res. September 2021 31: 1638-1645; Published in Advance July 20, 2021, doi:10.1101/gr.268599.120
...versus episomal encoding of enhancer activity. Genome Res 27: 38–52. doi:10.1101/gr.212092.116 ↵Kheradpour P, Ernst J, Melnikov A, Rogov P, Wang L, Zhang X, Alston J, Mikkelsen TS, Kellis M. 2013. Systematic dissection of regulatory motifs in 2000 predicted human enhancers using a massively parallel...
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Research: CG dinucleotides enhance promoter activity independent of DNA methylation
- Dominik Hartl,
- Arnaud R. Krebs,
- Ralph S. Grand,
- Tuncay Baubec,
- Luke Isbel,
- Christiane Wirbelauer,
- Lukas Burger,
- and Dirk Schübeler
Genome Res. April 2019 29: 554-563; Published in Advance February 1, 2019, doi:10.1101/gr.241653.118
...(ESCs). The resulting loss- and gain-of-function experiments reveal that CpGs contribute to transcriptional output independent of DNA methylation.ResultsParallel reporter assay at a defined chromosomal siteInvestigating CpG function necessitates an approach that systematically compares different...
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