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Research: Estrogen receptor 1 chromatin profiling in human breast tumors reveals high inter-patient heterogeneity with enrichment of risk SNPs and enhancer activity at most-conserved regions
- Stacey E.P. Joosten,
- Sebastian Gregoricchio,
- Suzan Stelloo,
- Elif Yapıcı,
- Chia-Chi Flora Huang,
- Kerim Yavuz,
- Maria Donaldson Collier,
- Tunç Morova,
- Umut Berkay Altintaş,
- Yongsoo Kim,
- Sander Canisius,
- Cathy B. Moelans,
- Paul J. van Diest,
- Gozde Korkmaz,
- Nathan A. Lack,
- Michiel Vermeulen,
- Sabine C. Linn,
- and Wilbert Zwart
Genome Res. April 2024 34: 539-555; Published in Advance May 6, 2024, doi:10.1101/gr.278680.123
...redundancy, may suggest a model in which the strongest EREs are more commonly bound and drive activation of the estrogen response, whereas “weaker” enhancers cooperate to maintain this transcriptional program, in support of a previously reported phase-separation model of ligand-activated enhancers (Nair et...
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Mini-Review: Revisiting models of enhancer–promoter communication in gene regulation
- Gilad Barshad and
- Charles G. Danko
Genome Res. June 2025 35: 1277-1286; doi:10.1101/gr.278389.123
...promoter and enhancer marks, existing data nevertheless support a model in which either the act of transcription or the sequence of the RNA is important for enhancer function.The stereotyped chromatin and transcriptional environment at enhancers is similar to that observed at active promoters, raising...
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Research: Estrogen-induced chromatin looping changes identify a subset of functional regulatory elements
- Hosiana Abewe,
- Alexandra Richey,
- Jeffery M. Vahrenkamp,
- Matthew Ginley-Hidinger,
- Craig M. Rush,
- Noel Kitchen,
- Xiaoyang Zhang,
- and Jason Gertz
Genome Res. March 2025 35: 393-403; Published in Advance March 3, 2025, doi:10.1101/gr.279699.124
...a gene's promoter or distal regions were correlated with larger transcriptional responses to estrogen compared with ERBSs not involved in differential 3D interactions. To functionally test this observation, CRISPR-based Enhancer-i was used to deactivate specific ERBSs, which revealed a wide range...
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Research: Enhancer RNA profiling predicts transcription factor activity
- Joseph G. Azofeifa,
- Mary A. Allen,
- Josephina R. Hendrix,
- Timothy Read,
- Jonathan D. Rubin,
- and Robin D. Dowell
Genome Res. March 2018 28: 334-344; Published in Advance February 15, 2018, doi:10.1101/gr.225755.117
...Department of Molecular, Cellular and Developmental Biology, 4Department of Biochemistry, University of Colorado, Boulder, Colorado 80309, USA Corresponding author: robin.dowell@colorado.eduAbstractTranscription factors (TFs) exert their regulatory influence through the binding of enhancers, resulting...
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Research: Global transcriptional activity dynamics reveal functional enhancer RNAs
- Yoon Jung Kim,
- Peng Xie,
- Lian Cao,
- Michael Q. Zhang,
- and Tae Hoon Kim
Genome Res. December 2018 28: 1799-1811; Published in Advance October 23, 2018, doi:10.1101/gr.233486.117
...a compendium of eRNA-producing enhancers responding to virus, then used HOMER (Heinz et al. 2010) to identify the eRNA transcripts (see Methods). Of 32,832 total intergenic transcripts, 11,025 transcripts overlapped with H3K4me1 or H3K27ac histone modification peaks, representative enhancer marks (Fig. 1A). We...
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Research: Enhancer transcription reveals subtype-specific gene expression programs controlling breast cancer pathogenesis
- Hector L. Franco,
- Anusha Nagari,
- Venkat S. Malladi,
- Wenqian Li,
- Yuanxin Xi,
- Dana Richardson,
- Kendra L. Allton,
- Kaori Tanaka,
- Jing Li,
- Shino Murakami,
- Khandan Keyomarsi,
- Mark T. Bedford,
- Xiaobing Shi,
- Wei Li,
- Michelle C. Barton,
- Sharon Y.R. Dent,
- and W. Lee Kraus
Genome Res. February 2018 28: 159-170; Published in Advance December 22, 2017, doi:10.1101/gr.226019.117
...is a defining feature of active enhancers, linking transcription factor (TF) binding to the molecular mechanisms controlling gene expression. To determine the relationship between enhancer activity and biological outcomes in breast cancers, we profiled the transcriptomes (using GRO-seq and RNA-seq) and epis...
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Research: Hormone-control regions mediate steroid receptor–dependent genome organization
- François Le Dily,
- Enrique Vidal,
- Yasmina Cuartero,
- Javier Quilez,
- A. Silvina Nacht,
- Guillermo P. Vicent,
- José Carbonell-Caballero,
- Priyanka Sharma,
- José Luis Villanueva-Cañas,
- Roberto Ferrari,
- Lara Isabel De Llobet,
- Gaetano Verde,
- Roni H.G. Wright,
- and Miguel Beato
Genome Res. January 2019 29: 29-39; Published in Advance December 14, 2018, doi:10.1101/gr.243824.118
...is dependent on the expression of the receptors and is further dynamically modulated in response to steroid hormones. HCRs function as platforms that integrate different signals, resulting in some cases in opposite transcriptional responses to estrogens or progestins. Altogether, these results suggest...
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Research: Transcription factor assisted loading and enhancer dynamics dictate the hepatic fasting response
- Ido Goldstein,
- Songjoon Baek,
- Diego M. Presman,
- Ville Paakinaho,
- Erin E. Swinstead,
- and Gordon L. Hager
Genome Res. March 2017 27: 427-439; Published in Advance December 28, 2016, doi:10.1101/gr.212175.116
...transcription (Shlyueva et al. 2014). Active enhancers show three key characteristics: (1) an increase in specific histone marks such as H3K27 acetylation (Creyghton et al. 2010); (2) enrichment of TF binding events; and (3) increased chromatin accessibility, measured by hypersensitivity to DNase I digestion...
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Research: Promoter-distal RNA polymerase II binding discriminates active from inactive CCAAT/ enhancer-binding protein beta binding sites
- Daniel Savic,
- Brian S. Roberts,
- Julia B. Carleton,
- E. Christopher Partridge,
- Michael A. White,
- Barak A. Cohen,
- Gregory M. Cooper,
- Jason Gertz,
- and Richard M. Myers
Genome Res. December 2015 25: 1791-1800; Published in Advance October 20, 2015, doi:10.1101/gr.191593.115
...; Ernst and Kellis 2010), promoter-distal RNAP2 occupancy (De Santa et al. 2010), enhancer RNA (eRNA) production (Hah et al. 2013; Li et al. 2013), and long-range looping interactions (Fullwood et al. 2009). Although these correlative genomic features allude to transcriptional roles, large...
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Research: GATA3 acts upstream of FOXA1 in mediating ESR1 binding by shaping enhancer accessibility
- Vasiliki Theodorou,
- Rory Stark,
- Suraj Menon,
- and Jason S. Carroll
Genome Res. January 2013 23: 12-22; Published in Advance November 21, 2012, doi:10.1101/gr.139469.112
...estrogen treatment. We find that GATA3 is pivotal in mediating enhancer accessibility at regulatory regions involved in ESR1-mediated transcription. GATA3 silencing resulted in a global redistribution of cofactors and active histone marks prior to estrogen stimulation. These global genomic changes altered...

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