The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
The Transcription Factor Runx3 Establishes Chromatin Accessibility of cis-Regulatory Landscapes that Drive Memory Cytotoxic T Lymphocyte Formation
Open accessAbstract
T cell receptor (TCR) stimulation of naive CD8+ T cells initiates reprogramming of cis-regulatory landscapes that specify effector and memory cytotoxic T lymphocyte (CTL) differentiation. We mapped regions of hyper-accessible chromatin in naive cells during TCR stimulation and discovered that the transcription factor (TF) Runx3 promoted accessibility to memory CTL-specific cis-regulatory regions before the first cell division and was essential for memory CTL differentiation. Runx3 was specifically required for accessibility to regions highly enriched with IRF, bZIP and Prdm1-like TF motifs, upregulation of TFs Irf4 and Blimp1, and activation of fundamental CTL attributes in early effector and memory precursor cells. Runx3 ensured that nascent CTLs differentiated into memory CTLs by preventing high expression of the TF T-bet, slowing effector cell proliferation, and repressing terminal CTL differentiation. Runx3 overexpression enhanced memory CTL differentiation during iterative infections. Thus, Runx3 governs chromatin accessibility during TCR stimulation and enforces the memory CTL developmental program.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Additionally, T RM cells can be identified by the upregulation of specific transcription factors such as HOBIT (homolog of Blimp-1 in T cells), RUNX3 (runt-related transcription factor 3), and BLIMP-1 (B lymphocyte-induced maturation protein-1), which lead to transcriptional reprogramming to downregulate tissue egress genes and upregulate tissue retention markers. 295-298”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [297]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709
clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters
Yu, G., Wang, L.-G., Han, Y., & He, Q.-Y. (2012) · OMICS: A Journal of Integrative Biology · doi:10.1089/omi.2011.0118 · Cited by 36,259
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386
Differential expression analysis for sequence count data
Anders, S., & Huber, W. (2010) · Genome Biology · doi:10.1186/gb-2010-11-10-r106 · Cited by 15,581
Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y., & Greenleaf, W. J. (2013) · Nature Methods · doi:10.1038/nmeth.2688 · Cited by 6,422
Meijer, L., Nelson, D. J., Riazanski, V., Gabdoulkhakova, A. G., Héry-Arnaud, G., Berre, R. L., Loaëc, N., Oumata, N., Galons, H., Nowak, E., et al. (2016) · Journal of Innate Immunity · doi:10.1159/000444256 · Cited by 5,008
Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus
Srinivas, S., Watanabe, T., Lin, C.-S., William, C. M., Tanabe, Y., Jessell, T. M., & Costantini, F. (2001) · BMC Developmental Biology · doi:10.1186/1471-213x-1-4 · Cited by 3,121
Joshi, N. S., Cui, W., Chandele, A., Lee, H. K., Urso, D. R., Hagman, J., Gapin, L., & Kaech, S. M. (2007) · Immunity · doi:10.1016/j.immuni.2007.07.010 · Cited by 1,861
Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin
Intlekofer, A. M., Takemoto, N., Wherry, E. J., Longworth, S. A., Northrup, J. T., Palanivel, V., Mullen, A. C., Gasink, C. R., Kaech, S. M., Miller, J. D., et al. (2005) · Nature Immunology · doi:10.1038/ni1268 · Cited by 1,293
Self-citationKaech, S. M., & Ahmed, R. (2001) · Nature Immunology · doi:10.1038/87720 · Cited by 1,265
van Stipdonk, M. J. B., Lemmens, E. E., & Schoenberger, S. P. (2001) · Nature Immunology · doi:10.1038/87730 · Cited by 843
Pipkin, M. E., Sacks, J. A., Cruz‐Guilloty, F., Lichtenheld, M. G., Bevan, M. J., & Rao, A. (2010) · Immunity · doi:10.1016/j.immuni.2009.11.012 · Cited by 817
Self-citationRuzankina, Y., Pinzon‐Guzman, C., Asare, A., Ong, T., Pontano, L. L., Cotsarelis, G., Zediak, V. P., Velez, M., Bhandoola, A., & Brown, E. J. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.03.002 · Cited by 803
Modulation of Chromatin Structure Regulates Cytokine Gene Expression during T Cell Differentiation
Agarwal, S., & Rao, A. (1998) · Immunity · doi:10.1016/s1074-7613(00)80642-1 · Cited by 688
Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours
Milner, J. J., Toma, C., Yu, B., Zhang, K., Omilusik, K., Phan, A. T., Wang, D., Getzler, A. J., Nguyen, T., Crotty, S., et al. (2017) · Nature · doi:10.1038/nature24993 · Cited by 677
Self-citationPioneer transcription factors in cell reprogrammingPreprint
Iwafuchi, M., & Zaret, K. S. (2014) · Genes & Development · doi:10.1101/gad.253443.114 · Cited by 613
Rutishauser, R. L., Martins, G. A., Kalachikov, S. M., Chandele, A., Parish, I. A., Meffre, E., Jacob, J., Calame, K. L., & Kaech, S. M. (2009) · Immunity · doi:10.1016/j.immuni.2009.05.014 · Cited by 612
Molecular regulation of effector and memory T cell differentiation
Chang, J. T., Wherry, E. J., & Goldrath, A. W. (2014) · Nature Immunology · doi:10.1038/ni.3031 · Cited by 604
Self-citationRunx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs
Cruz‐Guilloty, F., Pipkin, M. E., Djuretic, I. M., Levanon, D., Lotem, J., Lichtenheld, M. G., Groner, Y., & Rao, A. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20081242 · Cited by 518
Self-citationEffector CD8 T cells dedifferentiate into long-lived memory cells
Youngblood, B., Hale, J. S., Kissick, H. T., Ahn, E., Xu, X., Wieland, A., Araki, K., West, E. E., Ghoneim, H. E., Fan, Y., et al. (2017) · Nature · doi:10.1038/nature25144 · Cited by 481
Bhatt, D. M., Pandya‐Jones, A., Tong, A.-J., Barozzi, I., Lissner, M. M., Natoli, G., Black, D. L., & Smale, S. T. (2012) · Cell · doi:10.1016/j.cell.2012.05.043 · Cited by 447
Man, K., Miasari, M., Shi, W., Xin, A., Henstridge, D. C., Preston, S., Pellegrini, M., Belz, G. T., Smyth, G. K., Febbraio, M. A., et al. (2013) · Nature Immunology · doi:10.1038/ni.2710 · Cited by 412
Kurachi, M., Barnitz, R. A., Yosef, N., Odorizzi, P. M., DiIorio, M. A., Lemieux, M. E., Yates, K. B., Godec, J., Klatt, M. G., Regev, A., et al. (2014) · Nature Immunology · doi:10.1038/ni.2834 · Cited by 392
Levanon, D., Negreanu, V., Bernstein, Y., Bar-Am, I., Avivi, L., & Groner, Y. (1994) · Genomics · doi:10.1006/geno.1994.1519 · Cited by 391
Transcriptional insights into the CD8+ T cell response to infection and memory T cell formation
Best, J. A., Blair, D. A., Knell, J., Yang, E., Mayya, V., Doedens, A. L., Dustin, M. L., & Goldrath, A. W. (2013) · Nature Immunology · doi:10.1038/ni.2536 · Cited by 339
Self-citationAraki, Y., Wang, Z., Zang, C., Wood, W. H., Schones, D. E., Cui, K., Roh, T., Lhotsky, B., Wersto, R. P., Peng, W., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.05.006 · Cited by 331
Tahirov, T. H., Inoue-Bungo, T., Morii, H., Fujikawa, A., Sasaki, M., Kimura, K., Shiina, M., Sato, K., Kumasaka, T., Yamamoto, M., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00271-9 · Cited by 329
BACH2 regulates CD8+ T cell differentiation by controlling access of AP-1 factors to enhancers
Roychoudhuri, R., Clever, D. C., Li, P., Wakabayashi, Y., Quinn, K. M., Klebanoff, C. A., Ji, Y., Sukumar, M., Eil, R. L., Yu, Z., et al. (2016) · Nature Immunology · doi:10.1038/ni.3441 · Cited by 317
Dynamic Changes in Chromatin Accessibility Occur in CD8 + T Cells Responding to Viral Infection
Scott-Browne, J. P., López-Moyado, I. F., Trifari, S., Wong, V., Chávez, L., Rao, A., & Pereira, R. M. (2016) · Immunity · doi:10.1016/j.immuni.2016.10.028 · Cited by 317
Dominguez, C. X., Amezquita, R. A., Guan, T., Marshall, H. D., Joshi, N. S., Kleinstein, S. H., & Kaech, S. M. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20150186 · Cited by 275
Omilusik, K. D., Best, J. A., Yu, B., Goossens, S., Weidemann, A., Nguyen, J. V., Seuntjens, E., Stryjewska, A., Zweier, C., Roychoudhuri, R., et al. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20150194 · Cited by 260
Self-citationEpigenetic landscapes reveal transcription factors that regulate CD8+ T cell differentiation
Yu, B., Zhang, K., Milner, J. J., Toma, C., Chen, R., Scott-Browne, J. P., Pereira, R. M., Crotty, S., Chang, J. T., Pipkin, M. E., et al. (2017) · Nature Immunology · doi:10.1038/ni.3706 · Cited by 248
Self-citationImpact of artifact removal on ChIP quality metrics in ChIP-seq and ChIP-exo data
Carroll, T. S., Liang, Z., Salama, R. A., Stark, R., & de Santiago, I. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00075 · Cited by 247
Repression of interleukin-4 in T helper type 1 cells by Runx/Cbfβ binding to the Il4 silencer
Naoe, Y., Setoguchi, R., Akiyama, K., Muroi, S., Kuroda, M., Hatam, F., Littman, D. R., & Taniuchi, I. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20062456 · Cited by 242
Russ, B. E., Olshanksy, M., Smallwood, H. S., Li, J., Denton, A. E., Prier, J. E., Stock, A. T., McQuilten, H. A., Cullen, J. G., Nguyen, M. L. T., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.11.001 · Cited by 220
Different T Cell Receptor Signals Determine CD8 + Memory Versus Effector Development
Teixeiro, E., Daniëls, M. A., Hamilton, S. E., Schrum, A. G., Bragado, R., Jameson, S. C., & Palmer, E. (2009) · Science · doi:10.1126/science.1163612 · Cited by 199
Xin, A., Masson, F., Liao, Y., Preston, S., Guan, T., Gloury, R., Olshansky, M., Lin, J., Li, P., Speed, T. P., et al. (2016) · Nature Immunology · doi:10.1038/ni.3410 · Cited by 191
T Cell Fate at the Single-Cell Level
Buchholz, V. R., Schumacher, T. N., & Busch, D. H. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112014 · Cited by 158
Shan, Q., Zeng, Z., Xing, S., Li, F., Hartwig, S. M., Gullicksrud, J. A., Kurup, S. P., Budimir, N., Yao, S., Martin, M. D., et al. (2017) · Nature Immunology · doi:10.1038/ni.3773 · Cited by 157
Analysis of computational footprinting methods for DNase sequencing experiments
Gusmao, E. G., Allhoff, M., Zenke, M., & Costa, I. G. (2016) · Nature Methods · doi:10.1038/nmeth.3772 · Cited by 152
Zhang, D. J., Wang, Q., Wei, J., Baimukanova, G., Buchholz, F., Stewart, A. F., Mao, X., & Killeen, N. P. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.11.6725 · Cited by 132
Transcription Factor T-bet Regulates Intraepithelial Lymphocyte Functional Maturation
Reis, B. S., van Konijnenburg, D. P. H., Grivennikov, S. I., & Mucida, D. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.017 · Cited by 129
Chen, R., Bélanger, S., Frederick, M. A., Li, B., Johnston, R. J., Xiao, N., Liu, Y., Sharma, S., Peters, B., Rao, A., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.08.002 · Cited by 118
Self-citationHe, B., Xing, S., Chen, C., Gao, P., Li, T., Shan, Q., Gullicksrud, J. A., Martin, M. D., Yu, S., Harty, J. T., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.11.009 · Cited by 99
Raczkowski, F., Ritter, J., Heesch, K., Schumacher, V., Guralnik, A., Höcker, L., Raifer, H., Klein, M., Bopp, T., Harb, H., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1309378110 · Cited by 98
Cutting Edge: Chromatin Accessibility Programs CD8 T Cell Memory
Scharer, C. D., Bally, A. P. R., Gandham, B., & Boss, J. M. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1602086 · Cited by 82
Runx3-mediated Transcriptional Program in Cytotoxic Lymphocytes
Lotem, J., Levanon, D., Negreanu, V., Leshkowitz, D., Friedlander, G., & Groner, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080467 · Cited by 73
Plumlee, C. R., Obar, J. J., Colpitts, S. L., Jellison, E. R., Haining, W. N., Lefrançois, L., & Khanna, K. M. (2015) · Scientific Reports · doi:10.1038/srep12264 · Cited by 66
Ahmed, R., Byrne, J. A., & Oldstone, M. B. A. (1984) · Journal of Virology · doi:10.1128/jvi.51.1.34-41.1984 · Cited by 56
Bartfeld, D., Shimon, L. J. W., Couture, G. C., Rabinovich, D., Frolow, F., Levanon, D., Groner, Y., & Shakked, Z. (2002) · Structure · doi:10.1016/s0969-2126(02)00853-5 · Cited by 53
Chromosome Transfer Activates and Delineates a Locus Control Region for Perforin
Pipkin, M. E., Ljutic, B., Cruz‐Guilloty, F., Nouzová, M., Rao, A., Zúñiga‐Pflücker, J. C., & Lichtenheld, M. G. (2007) · Immunity · doi:10.1016/j.immuni.2006.11.009 · Cited by 39
Self-citationSeo, Y., Jothikumar, P., Suthar, M. S., Zhu, C., & Grakoui, A. (2016) · Immunity · doi:10.1016/j.immuni.2016.10.024 · Cited by 31
Pipkin, M. E. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl006 · Cited by 24
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling
Weber, E. W., Parker, K. R., Sotillo, E., Lynn, R. C., Anbunathan, H., Lattin, J., Good, Z., Belk, J. A., Dániel, B., Klysz, D. D., et al. (2021) · Science · doi:10.1126/science.aba1786 · Cited by 653
Crowl, J. T., Heeg, M., Ferry, A., Milner, J. J., Omilusik, K. D., Toma, C., He, Z., Chang, J. T., & Goldrath, A. W. (2022) · Nature Immunology · doi:10.1038/s41590-022-01229-8 · Cited by 253
Self-citationSingle-cell transcriptome profiling of an adult human cell atlas of 15 major organs
He, S., Wang, L.-H., Liu, Y., Li, Y., Chen, H.-T., Xu, J.-H., Peng, W., Lin, G.-W., Wei, P.-P., Li, B., et al. (2020) · Genome biology · doi:10.1186/s13059-020-02210-0 · Cited by 237
Self-citationThe precursors of CD8+ tissue resident memory T cells: from lymphoid organs to infected tissues
Kok, L., Masopust, D., & Schumacher, T. N. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-021-00590-3 · Cited by 230
RUNX transcription factors: orchestrators of development
Mevel, R., Draper, J. E., Lie-a-Ling, M., Kouskoff, V., & Lacaud, G. (2019) · Development · doi:10.1242/dev.148296 · Cited by 211
Metadata
- Authors
- Wang, D., Diao, H., Getzler, A. J., Rogal, W., Frederick, M. A., Milner, J., Yu, B., Crotty, S., Goldrath, A. W., & Pipkin, M. E.
- Affiliations
- Scripps Research Institute (US)
- University of California San Diego (US)
- La Jolla Institute for Immunology (US)
- Corresponding author
- Pipkin, Matthew E.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 48
- Issue
- 4
- Pages
- 659-674.e6
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC6750808
- OpenAlex
- W2800450153
- Cited by
- 201
- References
- 55
- Citations by year
- 2026: 16 · 2025: 29 · 2024: 19 · 2023: 31 · 2022: 29 · 2021: 32 · 2020: 27 · 2019: 12 · 2018: 6
- FWCI
- 9.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01 AI095634, NIH U19 AI109976)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- RUNX3, chromatin accessibility, cis-regulatory elements, T cell differentiation, T cell receptor stimulation, naive T cells, IRF4, Blimp-1, T-bet, effector T cells, transcription factor binding motifs, terminal differentiation
- MeSH terms
- Positive Regulatory Domain I-Binding Factor 1, Interferon Regulatory Factor-4, Animals, Binding Sites, Cell Differentiation, Cell Line, Chlorocebus aethiops, Chromatin, Enzyme Activation, Female, Cricetinae, Humans, Immunologic Memory, Male, Mice, Inbred C57BL, Receptors, Antigen, T-Cell, T-Lymphocytes, Cytotoxic, Vero Cells, Mice, Knockout, Cell Proliferation, Core Binding Factor Alpha 3 Subunit, Interferon Regulatory Factors, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
