ArticleMolecular cell2025
Widespread variation in molecular interactions and regulatory properties among transcription factor isoforms.
Abstract read
In one paragraph
Article in Molecular cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed.
- Large-scale single-molecule analysis of tau proteoforms.Nature methods · 2026Article
- Long-read proteogenomic atlas of human neuronal differentiation reveals isoform diversity informing neurodevelopmental risk mechanisms.Nature communications · 2026Article
- Aberrant splicing in human cancer shows possible functional impact on transcription factors.Oncogene · 2026Article
- Rhizome differentiation is associated with metabolic specialization and rhizosphere microbial assembly in Rheum officinale Baill.Plant cell reports · 2026Article
- Spatially resolved profiling of steroid nuclear receptors reveals a role for the disordered N-terminal domains in genome targeting and AP-1 interaction.Genome research · 2026Article
- Disease-associated genetic variants can cause missense effects in tissue-specific protein isoforms.Nature communications · 2026Article
- Transcription clusters and developmental pathways - nature, nurture, noise.Journal of cell science · 2026Review
- Construction of TF-lncRNA-miRNA-mRNA Regulatory Network Affecting Sow Reproduction Based on QTLs for Corpus Luteum Number.Animals : an open access journal from MDPI · 2026Article
- Distinct genetic architecture of gene and isoform level QTL in the Diversity Outbred (DO) mouse population.bioRxiv : the preprint server for biology · 2026Article
- Isoform-specific cofactor recruitment through the intrinsically disordered N-terminus of p63 underlies differential transcriptional activities.bioRxiv : the preprint server for biology · 2026Article
- Proteoform medicine: characterizing and targeting protein forms in human disease.Nature reviews. Genetics · 2026Review
- Efficient In Vivo Pharmacological Inhibition of ΔFOSB, an AP-1 Transcription Factor, in the Brain.ACS chemical neuroscience · 2026Article
- Disordered but rhythmic-the role of intrinsic protein disorder in eukaryotic circadian timing.FEBS letters · 2026Review
- Single-cell exon deletion profiling reveals splicing events that shape gene expression and cell state dynamics.Nature communications · 2026Article
- Isoforms in action: The impact of transcript diversity in phenotype.Genetics and molecular biology · 2026Article
- New p65 iso5 isoforms as dexamethasone-binding proteins: novel potential therapeutic targets for inflammatory diseases.Frontiers in immunology · 2026Article
- Long-read proteogenomic atlas of human neuronal differentiation reveals isoform diversity informing neurodevelopmental risk mechanisms.bioRxiv : the preprint server for biology · 2025Article
- Decoding cell fate: integrated experimental and computational analysis at the single-cell level.Bioinformatics (Oxford, England) · 2025Review
- ScIsoX: a multidimensional framework for measuring isoform-level transcriptomic complexity in single cells.Genome biology · 2025Article
- Topoisomerase I Inhibition in ETV4-overexpressed Non-Small Cell Lung Cancer Promotes Replication and Transcription Mediated R-Loop Accumulation and DNA Damage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
- Update of
Authors and funding
38 authors.
Luke LambourneCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Kaia MattioliDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: kaia.mattioli@gmail.com.
Clarissa SantosoDepartment of Biology, Boston University, Boston, MA 02215, USA; Bioinformatics Program, Boston University, Boston, MA 02215, USA.
Gloria SheynkmanCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Sachi InukaiDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Babita KaundalDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Anna BerensonMolecular Biology, Cell Biology & Biochemistry Program, Boston University, Boston, MA 02215, USA.
Kerstin Spirohn-FitzgeraldCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Anukana BhattacharjeeDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Elisabeth RothmanDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Shaleen ShresthaDepartment of Biology, Boston University, Boston, MA 02215, USA.
Florent LavalCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; TERRA Teaching and Research Centre, University of Liège, Gembloux 5030, Belgium; Laboratory of Viral Interactomes, GIGA Institute, University of Liège, Liège 4000, Belgium.
Brent S CarrollDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Stephen P PlassmeyerDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA; Center for Biomolecular Condensates, Washington University in St. Louis, St. Louis, MO 63110, USA.
Ryan J EmeneckerDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA; Center for Biomolecular Condensates, Washington University in St. Louis, St. Louis, MO 63110, USA.
Zhipeng YangCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Deepa BishtDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jared A SewellDepartment of Biology, Boston University, Boston, MA 02215, USA.
Guangyuan LiDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Anisa PrasadDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Harvard College, Cambridge, MA 02138, USA.
Sabrina PhanorDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Ryan LaneDepartment of Biology, Boston University, Boston, MA 02215, USA.
Devlin C MoyerBioinformatics Program, Boston University, Boston, MA 02215, USA.
Toby HuntEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CD10 1SD, UK.
Dawit BalchaCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Marinella GebbiaCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA; The Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E1, Canada; Lunenfeld-Tanenbaum Research Institute (LTRI), Sinai Health System, Toronto, ON M5G 1X5, Canada.
Jean-Claude TwizereCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA; TERRA Teaching and Research Centre, University of Liège, Gembloux 5030, Belgium; Laboratory of Viral Interactomes, GIGA Institute, University of Liège, Liège 4000, Belgium.
Tong HaoCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Alex S HolehouseDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA; Center for Biomolecular Condensates, Washington University in St. Louis, St. Louis, MO 63110, USA.
Adam FrankishEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CD10 1SD, UK.
Josh A RibackDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Nathan SalomonisDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Michael A CalderwoodCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
David E HillCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Nidhi SahniDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: nidhi.sahni.2025@gmail.com.
Marc VidalCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: marc_vidal@dfci.harvard.edu.
Martha L BulykCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: mlbulyk@genetics.med.harvard.edu.
Juan I Fuxman BassCenter for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biology, Boston University, Boston, MA 02215, USA; Bioinformatics Program, Boston University, Boston, MA 02215, USA; Molecular Biology, Cell Biology & Biochemistry Program, Boston University, Boston, MA 02215, USA. Electronic address: fuxman@bu.edu.
Funding
GENCODE: comprehensive reference genome annotation for human and mouseU24HG007234 · NHGRI · EUROPEAN MOLECULAR BIOLOGY LABORATORY · PI Fergal James Martin · 2021 to 2026
$16.1MTumor Cell Biology Training ProgramT32CA009361 · NCI · DANA-FARBER CANCER INSTITUTE · PI GRAY, NATHANAEL SCHIANDER · 1985 to 2015
$8.9MRewiring of regulatory networks in breast cancer by transcription factor isoformsU01CA232161 · NCI · DANA-FARBER CANCER INST · PI BULYK, MARTHA L, FUXMAN BASS, JUAN IGNACIO · 2018 to 2022
$4.1MStructure and Function of Immune Gene Regulatory NetworksR35GM128625 · NIGMS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI Juan Ignacio Fuxman Bass · 2018 to 2026
$4.0MGenerating a full-length reference transcriptome for human protein-coding genesU24HG011451 · NHGRI · DANA-FARBER CANCER INST · PI David E. Hill, Marc Vidal · 2022 to 2026
$3.3MUnbiased identification of spliceosome vulnerabilities across cancerR01CA226802 · NCI · CINCINNATI CHILDRENS HOSP MED CTR · PI SALOMONIS, NATHAN G. · 2018 to 2022
$2.4MUncovering the regulatory logic of gene expression encoded by disordered regionsDP2CA290639 · NCI · WASHINGTON UNIVERSITY · PI Alex S Holehouse · 2023 to 2026
$2.3MUncovering the functional diversification mechanisms of transcription factor isoforms involved in stem cell differentiationR35GM142647 · NIGMS · UNIVERSITY OF VIRGINIA · PI SHEYNKMAN, GLORIA · 2021 to 2025
$2.1MDeciphering Functional Consequences of Specific and Combinatorial Mutations in Protein Interaction NetworksR35GM137836 · NIGMS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SAHNI, NIDHI · 2020 to 2023
$1.8MFunctional genomics approaches to decode the roles of transcription factor isoformsK99HG013345 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI MATTIOLI, KAIA · 2024 to 2025
$254kDecoding the role of transcription factor isoformsF32HG012318 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI MATTIOLI, KAIA · 2022 to 2023
$109kNCI NIH HHS DP2 CA290639NCI NIH HHS R01 CA226802NCI NIH HHS T32 CA009361NCI NIH HHS U01 CA232161NHGRI NIH HHS F32 HG012318NHGRI NIH HHS K99 HG013345NHGRI NIH HHS U24 HG007234NHGRI NIH HHS U24 HG011451NIGMS NIH HHS R35 GM128625NIGMS NIH HHS R35 GM137836NIGMS NIH HHS R35 GM142647
Abstract
Most human transcription factor (TF) genes encode multiple protein isoforms differing in DNA-binding domains, effector domains, or other protein regions. The global extent to which this results in functional differences between isoforms remains unknown. Here, we systematically compared 693 isoforms of 246 TF genes, assessing DNA binding, protein binding, transcriptional activation, subcellular localization, and condensate formation. Relative to reference isoforms, two-thirds of alternative TF isoforms exhibit differences in one or more molecular activities, which often could not be predicted from sequence. We observed two primary categories of alternative TF isoforms: "rewirers" and "negative regulators," both of which were associated with differentiation and cancer. Our results support a model wherein the relative expression levels of, and interactions involving, TF isoforms add an understudied layer of complexity to gene regulatory networks, demonstrating the importance of isoform-aware characterization of TF functions and providing a rich resource for further studies.
Indexed as
Gene Regulatory NetworksTranscription FactorsAlternative SplicingHumansNeoplasmsProtein BindingProtein IsoformsTranscriptional ActivationProtein IsoformsTranscription Factorsalternative splicinggene regulationisoformstranscriptional regulationtranscription factors
Identifiers
What Socratic holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.