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Research: Ultra-long-range interactions between active regulatory elements
- Elias T. Friman,
- Ilya M. Flyamer,
- Davide Marenduzzo,
- Shelagh Boyle,
- and Wendy A. Bickmore
Genome Res. August 2023 33: 1269-1283; Published in Advance July 14, 2023, doi:10.1101/gr.277567.122
...embryonic stem cells (mESCs) and differentiated cell types, active transcription start sites (TSSs) and transcription factor (TF) binding sites have been shown to interact with their own type across 2–10 Mb (Bonev et al. 2017). The function of, and processes driving, these long-range interactions...
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Research: Functional genomics analysis of developing zebrafish and human endoderm reveals highly conserved cis-regulatory modules acting during vertebrate organogenesis
- Daniela M. Riley,
- Randa Elsayed,
- Mark D. Walsh,
- Simaran Johal,
- Ying Lin,
- Harry Walton,
- Till Bretschneider,
- Sascha Ott,
- and Andrew C. Nelson
Genome Res. March 4, 2026 ; Published in Advance March 4, 2026, doi:10.1101/gr.280838.125
..., potentially suggesting function across these distinct organ systems. Additionally, we identify highly conserved CRMs potentially participating in endodermal patterning of adjacent craniofacial structures and sensory tissues. The highly conserved CRMs we identify are characterized by conserved patterns...
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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
...on potentially misleading predictions.Prediction of potential regulatory sitesThis review focuses on gene-specific transcriptional regulation via direct TF binding to regulatory DNA sites. The initial task is thus to locate candidate DNA regions potentially involved in TF binding, and this starts...
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Research: Widespread roles of enhancer-like transposable elements in cell identity and long-range genomic interactions
- Yaqiang Cao,
- Guoyu Chen,
- Gang Wu,
- Xiaoli Zhang,
- Joseph McDermott,
- Xingwei Chen,
- Chi Xu,
- Quanlong Jiang,
- Zhaoxiong Chen,
- Yingying Zeng,
- Daosheng Ai,
- Yi Huang,
- and Jing-Dong J. Han
Genome Res. January 2019 29: 40-52; Published in Advance November 19, 2018, doi:10.1101/gr.235747.118
...and L2 elements frequently share long-range intra-chromosomal interactions and binding of physically interacting transcription factors. We validated that eight L2 and nine MIR elements function as enhancers in reporter assays, and among 20 MIR-L2 pairings, one MIR repressed and one boosted the enhancer...
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Method: The oligogenic inheritance test GCOD detects risk genes and their interactions in congenital heart defects
- Maureen Pittman,
- Kihyun Lee,
- Franco Felix,
- Yu Huang,
- Adrienne Lam,
- Mauro W. Costa,
- Deepak Srivastava,
- and Katherine S. Pollard
Genome Res. February 2026 36: 330-347; Published in Advance December 12, 2025, doi:10.1101/gr.281141.125
...percentile (Supplemental Fig. 3A). However, similar to known CHD genes, our new GCOD candidates are not restricted to being active in heart development and show broad expression across cell types and tissues. Based on data from the Protein Atlas (Uhlén et al. 2015; Karlsson et al. 2021), both known CHD genes...
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Research: Clustered and diverse transcription factor binding underlies cell type specificity of enhancers for housekeeping genes
- Iris Zhu and
- David Landsman
Genome Res. October 2023 33: 1662-1672; Published in Advance October 26, 2023, doi:10.1101/gr.278130.123
...tissues. Here we report that most of the commonly expressed mouse or human genes across different cell types, including more than half of the previously identified housekeeping genes, are associated with cell type–specific enhancers. Furthermore, the binding of most transcription factors (TFs) is cell...
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Research: Wnt signaling activation induces CTCF binding and loop formation at cis-regulatory elements of target genes
- Anna Nordin,
- Chaitali Chakraborty,
- Mattias Jonasson,
- Orgena Dano,
- Gianluca Zambanini,
- Pierfrancesco Pagella,
- Silvia Remeseiro,
- and Claudio Cantù
Genome Res. August 2025 35: 1701-1716; Published in Advance June 23, 2025, doi:10.1101/gr.279684.124
...or facilitate such interactions, with long-range interactions being more dependent on CTCF than short-range interactions (Andrey et al. 2017). Even small changes in CTCF binding patterns can affect local gene regulation during stem cell differentiation (Su et al. 2021), epithelial-to-mesenchymal transition...
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Resource: Integrated single-cell multiome analysis reveals muscle fiber-type gene regulatory circuitry modulated by endurance exercise
- Aliza B. Rubenstein,
- Gregory R. Smith,
- Zidong Zhang,
- Xi Chen,
- Toby L. Chambers,
- Frederique Ruf-Zamojski,
- Natalia Mendelev,
- Wan Sze Cheng,
- Michel Zamojski,
- Mary Anne S. Amper,
- Venugopalan D. Nair,
- Andrew R. Marderstein,
- Stephen B. Montgomery,
- Olga G. Troyanskaya,
- Elena Zaslavsky,
- Todd Trappe,
- Scott Trappe,
- and Stuart C. Sealfon
Genome Res. July 2025 35: 1664-1677; Published in Advance May 20, 2025, doi:10.1101/gr.280051.124
...)-expressing fibro-adipogenic progenitor cells. Single-cell regulatory circuit triad reconstruction (transcription factor, chromatin interaction site, regulated gene) also identifies largely distinct gene regulatory circuits modulated by exercise in the three muscle fiber types and LUM-expressing fibro...
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Research: A DNA methylation haplotype block landscape in human tissues and preimplantation embryos reveals regulatory elements defined by comethylation patterns
- Yan Feng,
- Zhiqiang Zhang,
- Yuyang Hong,
- Yi Ding,
- Leiqin Liu,
- Siqi Gao,
- Hai Fang,
- and Jiantao Shi
Genome Res. December 2023 33: 2041-2052; Published in Advance November 8, 2023, doi:10.1101/gr.278146.123
...CRELD1 (Chr 3: 9,969,000–9,995,000), which ChIA-PET indicated contacts the promoter region through long-range interactions. This MHB showed partial methylation and was flanked by HMRs (Fig. 2D).To further investigate the regulatory roles of MHBs, we examined the overlap of tissue MHBs with annotations...
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Research: An AR-ERG transcriptional signature defined by long-range chromatin interactomes in prostate cancer cells
- Zhizhuo Zhang,
- Kern Rei Chng,
- Shreyas Lingadahalli,
- Zikai Chen,
- Mei Hui Liu,
- Huy Hoang Do,
- Shaojiang Cai,
- Nicola Rinaldi,
- Huay Mei Poh,
- Guoliang Li,
- Ying Ying Sung,
- Charlie L. Heng,
- Leighton J. Core,
- Si Kee Tan,
- Xiaoan Ruan,
- John T. Lis,
- Manolis Kellis,
- Yijun Ruan,
- Wing-Kin Sung,
- and Edwin Cheung
Genome Res. February 2019 29: 223-235; Published in Advance January 3, 2019, doi:10.1101/gr.230243.117
...that chromatin interaction data are critical for elucidating the long-range gene regulatory mechanisms.ERG is involved in AR-associated chromatin interactionsCo-TFs work together with nuclear hormone receptors to coordinate different steps in the transcription process, including long-range chromatin interaction...

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