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Research: A gene regulatory element modulates myosin expression and controls cardiomyocyte response to stress
- Taylor Anglen,
- Irene M. Kaplow,
- Baekgyu Choi,
- Enya Dewars,
- Robin M. Perelli,
- Kevin T. Hagy,
- Duc Tran,
- Megan E. Ramaker,
- Svati H. Shah,
- Inkyung Jung,
- Andrew P. Landstrom,
- Ravi Karra,
- Yarui Diao,
- and Charles A. Gersbach
Genome Res. November 2025 35: 2418-2432; Published in Advance October 22, 2025, doi:10.1101/gr.280825.125
...conformation assays in combination with epi editing, we find that gene regulation is mediated by a direct interaction between MYH6 and the enhancer. We also find that enhancer activation alters cardiomyocyte response to the hypertrophy-inducing peptide endothelin-1. Enhancer activation prevents...
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Research: Transcriptional regulatory dynamics drive coordinated metabolic and neural response to social challenge in mice
- Michael C. Saul,
- Christopher H. Seward,
- Joseph M. Troy,
- Huimin Zhang,
- Laura G. Sloofman,
- Xiaochen Lu,
- Patricia A. Weisner,
- Derek Caetano-Anolles,
- Hao Sun,
- Sihai Dave Zhao,
- Sriram Chandrasekaran,
- Saurabh Sinha,
- and Lisa Stubbs
Genome Res. June 2017 27: 959-972; Published in Advance March 29, 2017, doi:10.1101/gr.214221.116
...regulator ofWnt (Auld et al. 2012), andWnt intersects with ESRRAon both metabolic and behavioral axes. Notably, mutations in the Wnt effector, Tcf7l2, are associatedwith abnormal insulin and glucose homeostasis as well as deficits in fear learning (for review, see Nobrega 2013). Tcf7l2 is one of a small...
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Method: Targeted single-cell RNA sequencing of transcription factors enhances the identification of cell types and trajectories
- Alexandra Pokhilko,
- Adam E. Handel,
- Fabiola Curion,
- Viola Volpato,
- Emma S. Whiteley,
- Sunniva Bøstrand,
- Sarah E. Newey,
- Colin J. Akerman,
- Caleb Webber,
- Michael B. Clark,
- Rory Bowden,
- and M. Zameel Cader
Genome Res. June 2021 31: 1069-1081; Published in Advance May 19, 2021, doi:10.1101/gr.273961.120
...revealed that cells of the glial-like cell cluster G express TFs that included HES1, HES5, PAX6, NR2E1, TCF7L2, OTX1, as well as GFAP, consistent with a radial glial or proliferative neural progenitor identity (Supplemental Fig. S5; Darmanis et al. 2015; Telley et al. 2016). This was unexpected, because...
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Method: Deep profiling and custom databases improve detection of proteoforms generated by alternative splicing
- Laura M. Agosto,
- Matthew R. Gazzara,
- Caleb M. Radens,
- Simone Sidoli,
- Josue Baeza,
- Benjamin A. Garcia,
- and Kristen W. Lynch
Genome Res. December 2019 29: 2046-2055; Published in Advance November 14, 2019, doi:10.1101/gr.248435.119
...controls.In addition to observing distinct proteoforms, we can also quantify differential expression between alternate proteoforms. A clear example of this is the differential expression of alternate isoforms of the metabolic kinase PKM. PKM transcripts have been previously shown to be regulated by AS...
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Research: Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma
- Zhengyan Kan,
- Hancheng Zheng,
- Xiao Liu,
- Shuyu Li,
- Thomas D. Barber,
- Zhuolin Gong,
- Huan Gao,
- Ke Hao,
- Melinda D. Willard,
- Jiangchun Xu,
- Robert Hauptschein,
- Paul A. Rejto,
- Julio Fernandez,
- Guan Wang,
- Qinghui Zhang,
- Bo Wang,
- Ronghua Chen,
- Jian Wang,
- Nikki P. Lee,
- Wei Zhou,
- Zhao Lin,
- Zhiyu Peng,
- Kang Yi,
- Shengpei Chen,
- Lin Li,
- Xiaomei Fan,
- Jie Yang,
- Rui Ye,
- Jia Ju,
- Kai Wang,
- Heather Estrella,
- Shibing Deng,
- Ping Wei,
- Ming Qiu,
- Isabella H. Wulur,
- Jiangang Liu,
- Mariam E. Ehsani,
- Chunsheng Zhang,
- Andrey Loboda,
- Wing Kin Sung,
- Amit Aggarwal,
- Ronnie T. Poon,
- Sheung Tat Fan,
- Jun Wang,
- James Hardwick,
- Christoph Reinhard,
- Hongyue Dai,
- Yingrui Li,
- John M. Luk,
- and Mao Mao
Genome Res. September 2013 23: 1422-1433; Published in Advance June 20, 2013, doi:10.1101/gr.154492.113
...was represented as a percentage of all cases harboring a genomic alteration in one of the pathway genes shown. Gene expression up- or down-regulation in tumor relative to normal samples is shown but not included in the calculation of alteration frequencies. Alteration types and frequencies were represented...
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Research: Genome-wide analysis of histone modifications in human pancreatic islets
- Reena Bhandare,
- Jonathan Schug,
- John Le Lay,
- Alan Fox,
- Olga Smirnova,
- Chengyang Liu,
- Ali Naji,
- and Klaus H. Kaestner
Genome Res. April 2010 20: 428-433; Published in Advance February 24, 2010, doi:10.1101/gr.102038.109
...-Intergenic 4 506 rs4712523-CDKAL1 6 424 rs4712524-CDKAL1 6 424 rs2647044-HLA-E 6 181 rs9472138-VEGFA 6 839 rs13266634-SLC30A8 8 599 rs7903146-TCF7L2 10 120 rs5215-KCNJ11 11 762 rs5219-KCNJ11 11 1053 rs2292239-ERBB3 12 427 rs3184504-SH2B3 12 736 rs2903692-KIAA0350a 16 1064 rs8050136-FTO 16 1271 rs425105...
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Perspective: Genetic architecture of quantitative traits in mice, flies, and humans
- Jonathan Flint and
- Trudy F.C. Mackay
Genome Res. May 2009 19: 723-733; doi:10.1101/gr.086660.108
...in TCF7L2 are associated with both type 2 diabetes (Grant et al. 2006) and colon cancer (Slattery et al. 2008); SNPs in JAZF1 are associated with both type 2 diabetes (Zeggini et al. 2008) and prostate cancer (Thomas et al. 2008). How much does genetic architecture vary between phenotypes? Evidence from...

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