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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
...by the coding region (exons and introns); and ending with a terminator and polyadenylation signals that ensure proper transcript processing and stability. Before we can determine proteins that directly regulate GOI expression, we must identify the regulatory DNA sequences relevant to the GOI such as its...
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Research: Characterization of functional relationships of R-loops with gene transcription and epigenetic modifications in rice
- Yuan Fang,
- Lifen Chen,
- Kande Lin,
- Yilong Feng,
- Pengyue Zhang,
- Xiucai Pan,
- Jennifer Sanders,
- Yufeng Wu,
- Xiu-e Wang,
- Zhen Su,
- Caiyan Chen,
- Hairong Wei,
- and Wenli Zhang
Genome Res. August 2019 29: 1287-1297; Published in Advance July 1, 2019, doi:10.1101/gr.246009.118
...validation provided evidence that the demethylation of both DNA and histone marks can influence R-loop peak levels on a -wide scale. This is the first study in plants that reveals novel functional aspects of R-loops, their interrelations with epigenetic methylation, and roles in transcriptional regulation...
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Research: GC skew defines distinct RNA polymerase pause sites in CpG island promoters
- Wendy A. Kellner,
- Joshua S.K. Bell,
- and Paula M. Vertino
Genome Res. November 2015 25: 1600-1609; Published in Advance August 14, 2015, doi:10.1101/gr.189068.114
...supporting the idea that divergent transcription, GC skew/ R-loop formation, and Pol II pausing are inextricably linked and conspire tomaintain the unique epigenetic environment of CGI domains. Methods Data sets used in this study The following data sets were used in this study: for MCF7 cells, Ch...
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Research: Ligand-induced native G-quadruplex stabilization impairs transcription initiation
- Conghui Li,
- Honghong Wang,
- Zhinang Yin,
- Pingping Fang,
- Ruijing Xiao,
- Ying Xiang,
- Wen Wang,
- Qiuzi Li,
- Beili Huang,
- Jian Huang,
- and Kaiwei Liang
Genome Res. September 2021 31: 1546-1560; Published in Advance August 16, 2021, doi:10.1101/gr.275431.121
...RNA 3′ ends and maps transcriptionally engaged Pol II. G4 signals overlapped with the TSSs and Pol II pausing sites at promoter regions (Fig. 1I,J), indicating that G4s may participate in the early stages of transcription.Because G4-CUT&Tag could detect the G4 signals at enhancers (Fig. 1E), we...
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Research: Nascent RNA folding mitigates transcription-associated mutagenesis
- Xiaoshu Chen,
- Jian-Rong Yang,
- and Jianzhi Zhang
Genome Res. January 2016 26: 50-59; Published in Advance October 30, 2015, doi:10.1101/gr.195164.115
...author: jianzhi@umich.edu Abstract Transcription is mutagenic, in part because the R-loop formed by the binding of the nascent RNA with its DNA template exposes the nontemplate DNA strand to mutagens and primes unscheduled error-prone DNA synthesis. We hypothesize that strong folding...
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Research: De novo DNA demethylation and noncoding transcription define active intergenic regulatory elements
- Felix Schlesinger,
- Andrew D. Smith,
- Thomas R. Gingeras,
- Gregory J. Hannon,
- and Emily Hodges
Genome Res. October 2013 23: 1601-1614; Published in Advance June 28, 2013, doi:10.1101/gr.157271.113
...motifs of lymphoid-specific TFs at B cell iHMRs (Hodges et al. 2011). In addition, recent work has shown that binding of some transcription factors is directly linked to intergenic hypomethylation (Stadler et al. 2011). Therefore, we hypothesized that these iHMRs designate a lymphoid lineagespecific...
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Research: Genome-wide mapping reveals R-loops associated with centromeric repeats in maize
- Yang Liu,
- Qian Liu,
- Handong Su,
- Kunpeng Liu,
- Xue Xiao,
- Wei Li,
- Qianwen Sun,
- James A. Birchler,
- and Fangpu Han
Genome Res. August 2021 31: 1409-1418; Published in Advance July 9, 2021, doi:10.1101/gr.275270.121
...a -wide identification of R-loops and identified more than 700,000 R-loop peaks in the maize (Zea mays) . We found that sense R-loops were mainly enriched in promoters and transcription termination sites and relatively less enriched in gene bodies, which is different from the main gene-body localization...
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Research: The asymmetric distribution of RNA polymerase II and nucleosomes on replicated daughter genomes is caused by differences in replication timing between the lagging and the leading strand
- Rahima Ziane,
- Alain Camasses,
- and Marta Radman-Livaja
Genome Res. February 2022 32: 337-356; Published in Advance January 18, 2022, doi:10.1101/gr.275387.121
...5535, CNRS, 34293 Montpellier Cedex 5, France; 2Université de Montpellier, 34090 Montpellier, France Corresponding author: marta.radman-livaja@igmm.cnrs.frAbstractChromatin features are thought to have a role in the epigenetic transmission of transcription states from one cell generation to the next...
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Mini-Review: The paradox of R-loops: guardians of the genome or drivers of disease?
- Shachinthaka D. Dissanayaka Mudiyanselage,
- Phillip Wulfridge,
- and Kavitha Sarma
Genome Res. September 2025 35: 1919-1928; Published in Advance August 6, 2025, doi:10.1101/gr.278992.124
...with the G/C skew that is typically seen in R-loops and an enrichment of signal at transcription pause sites. Interestingly, unlike DRIP-seq, R-ChIP did not show R-loop presence at transcription termination sites, suggesting that S9.6 and RNase H may selectively recognize distinct features within R-loops...
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Research: H3S10ph broadly marks early-replicating domains in interphase ESCs and shows reciprocal antagonism with H3K9me2
- Carol C.L. Chen,
- Preeti Goyal,
- Mohammad M. Karimi,
- Marie H. Abildgaard,
- Hiroshi Kimura,
- and Matthew C. Lorincz
Genome Res. January 2018 28: 37-51; Published in Advance December 11, 2017, doi:10.1101/gr.224717.117
..., these results indicate that within TTRs, EHMT2/EHMT1 play a role in regulating transcription units co-oriented with the gross direction of DNA replication.As EHMT2-dependent H3K9me2 was reported to mediate Pol II transcriptional termination via R-loop formation (Skourti-Stathaki et al. 2014), we considered...

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