Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

The Roles of RUNX Family Proteins in Development of Immune Cells

  • Seo, Wooseok (Department of Immunology, Nagoya University Graduate School of Medicine) ;
  • Taniuchi, Ichiro (Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences)
  • Received : 2019.11.26
  • Accepted : 2019.12.12
  • Published : 2020.02.29
Download PDF
⟨ Previous Next ⟩

Abstract

The Runt-related transcription factors (RUNX) transcription factors have been known for their critical roles in numerous developmental processes and diseases such as autoimmune disorders and cancer. Especially, RUNX proteins are best known for their roles in hematopoiesis, particularly during the development of T cells. As scientists discover more types of new immune cells, the functional diversity of RUNX proteins also has been increased over time. Furthermore, recent research has revealed complicated transcriptional networks involving RUNX proteins by the current technical advances. Databases established by next generation sequencing data analysis has identified ever increasing numbers of potential targets for RUNX proteins and other transcription factors. Here, we summarize diverse functions of RUNX proteins mainly on lymphoid lineage cells by incorporating recent discoveries.

Keywords

References

  1. Bruno, L., Mazzarella, L., Hoogenkamp, M., Hertweck, A., Cobb, B.S., Sauer, S., Hadjur, S., Leleu, M., Naoe, Y., Telfer, J.C., et al. (2009). Runx proteins regulate Foxp3 expression. J. Exp. Med. 206, 2329-2337. https://doi.org/10.1084/jem.20090226
  2. Cooper, M.A., Elliott, J.M., Keyel, P.A., Yang, L., Carrero, J.A., and Yokoyama, W.M. (2009). Cytokine-induced memory-like natural killer cells. Proc. Natl. Acad. Sci. U. S. A. 106, 1915-1919. https://doi.org/10.1073/pnas.0813192106
  3. Cruz-Guilloty, F., Pipkin, M.E., Djuretic, I.M., Levanon, D., Lotem, J., Lichtenheld, M.G., Groner, Y., and Rao, A. (2009). Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs. J. Exp. Med. 206, 51-59. https://doi.org/10.1084/jem.20081242
  4. Djuretic, I.M., Levanon, D., Negreanu, V., Groner, Y., Rao, A., and Ansel, K.M. (2007). Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells. Nat. Immunol. 8, 145-153. https://doi.org/10.1038/ni1424
  5. Egawa, T., Eberl, G., Taniuchi, I., Benlagha, K., Geissmann, F., Hennighausen, L., Bendelac, A., and Littman, D.R. (2005). Genetic evidence supporting selection of the Valpha14i NKT cell lineage from double-positive thymocyte precursors. Immunity 22, 705-716. https://doi.org/10.1016/j.immuni.2005.03.011
  6. Egawa, T., Tillman, R.E., Naoe, Y., Taniuchi, I., and Littman, D.R. (2007). The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells. J. Exp. Med. 204, 1945-1957. https://doi.org/10.1084/jem.20070133
  7. Growney, J.D., Shigematsu, H., Li, Z., Lee, B.H., Adelsperger, J., Rowan, R., Curley, D.P., Kutok, J.L., Akashi, K., Williams, I.R., et al. (2005). Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype. Blood 106, 494-504.
  8. Guo, H. and Friedman, A.D. (2011). Phosphorylation of RUNX1 by cyclindependent kinase reduces direct interaction with HDAC1 and HDAC3. J. Biol. Chem. 286, 208-215. https://doi.org/10.1074/jbc.M110.149013
  9. Guo, Y., Maillard, I., Chakraborti, S., Rothenberg, E.V., and Speck, N.A. (2008). Core binding factors are necessary for natural killer cell development and cooperate with Notch signaling during T-cell specification. Blood 112, 480-492.
  10. Ha-Lee, Y.M., Lee, Y., Kim, Y.K., and Sohn, J. (2000). Cross-linking of CD4 induces cytoskeletal association of CD4 and p56lck. Exp. Mol. Med. 32, 18-22. https://doi.org/10.1038/emm.2000.4
  11. Hanai, J., Chen, L.F., Kanno, T., Ohtani-Fujita, N., Kim, W.Y., Guo, W.H., Imamura, T., Ishidou, Y., Fukuchi, M., Shi, M.J., et al. (1999). Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Calpha promoter. J. Biol. Chem. 274, 31577-31582. https://doi.org/10.1074/jbc.274.44.31577
  12. Ichikawa, M., Asai, T., Saito, T., Seo, S., Yamazaki, I., Yamagata, T., Mitani, K., Chiba, S., Ogawa, S., Kurokawa, M., et al. (2004). AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis. Nat. Med. 10, 299-304. https://doi.org/10.1038/nm997
  13. Ito, Y., Bae, S.C., and Chuang, L.S. (2015). The RUNX family: developmental regulators in cancer. Nat. Rev. Cancer 15, 81-95. https://doi.org/10.1038/nrc3877
  14. Jin, Y.H., Jeon, E.J., Li, Q.L., Lee, Y.H., Choi, J.K., Kim, W.J., Lee, K.Y., and Bae, S.C. (2004). Transforming growth factor-beta stimulates p300-dependent RUNX3 acetylation, which inhibits ubiquitination-mediated degradation. J. Biol. Chem. 279, 29409-29417. https://doi.org/10.1074/jbc.M313120200
  15. Kamimura, Y. and Lanier, L.L. (2015). Homeostatic control of memory cell progenitors in the natural killer cell lineage. Cell Rep. 10, 280-291. https://doi.org/10.1016/j.celrep.2014.12.025
  16. Kim, J.H., Jang, J.W., Lee, Y.S., Lee, J.W., Chi, X.Z., Li, Y.H., Kim, M.K., Kim, D.M., Choi, B.S., Kim, J., et al. (2014). RUNX family members are covalently modified and regulated by PIAS1-mediated sumoylation. Oncogenesis 3, e101. https://doi.org/10.1038/oncsis.2014.15
  17. Kim, W.Y., Sieweke, M., Ogawa, E., Wee, H.J., Englmeier, U., Graf, T., and Ito, Y. (1999). Mutual activation of Ets-1 and AML1 DNA binding by direct interaction of their autoinhibitory domains. EMBO J. 18, 1609-1620. https://doi.org/10.1093/emboj/18.6.1609
  18. Kitagawa, Y., Ohkura, N., Kidani, Y., Vandenbon, A., Hirota, K., Kawakami, R., Yasuda, K., Motooka, D., Nakamura, S., Kondo, M., et al. (2017). Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment. Nat. Immunol. 18, 173-183. https://doi.org/10.1038/ni.3646
  19. Kitoh, A., Ono, M., Naoe, Y., Ohkura, N., Yamaguchi, T., Yaguchi, H., Kitabayashi, I., Tsukada, T., Nomura, T., Miyachi, Y., et al. (2009). Indispensable role of the Runx1-Cbfbeta transcription complex for in vivosuppressive function of FoxP3+ regulatory T cells. Immunity 31, 609-620. https://doi.org/10.1016/j.immuni.2009.09.003
  20. Komine, O., Hayashi, K., Natsume, W., Watanabe, T., Seki, Y., Seki, N., Yagi, R., Sukzuki, W., Tamauchi, H., Hozumi, K., et al. (2003). The Runx1 transcription factor inhibits the differentiation of naive CD4+ T cells into the Th2 lineage by repressing GATA3 expression. J. Exp. Med. 198, 51-61. https://doi.org/10.1084/jem.20021200
  21. Komori, T., Yagi, H., Nomura, S., Yamaguchi, A., Sasaki, K., Deguchi, K., Shimizu, Y., Bronson, R.T., Gao, Y.H., Inada, M., et al. (1997). Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89, 755-764. https://doi.org/10.1016/S0092-8674(00)80258-5
  22. Levanon, D., Bettoun, D., Harris-Cerruti, C., Woolf, E., Negreanu, V., Eilam, R., Bernstein, Y., Goldenberg, D., Xiao, C., Fliegauf, M., et al. (2002). The Runx3 transcription factor regulates development and survival of TrkC dorsal root ganglia neurons. EMBO J. 21, 3454-3463. https://doi.org/10.1093/emboj/cdf370
  23. Levanon, D., Negreanu, V., Lotem, J., Bone, K.R., Brenner, O., Leshkowitz, D., and Groner, Y. (2014). Transcription factor Runx3 regulates interleukin-15-dependent natural killer cell activation. Mol. Cell. Biol. 34, 1158-1169. https://doi.org/10.1128/MCB.01202-13
  24. Maier, H., Ostraat, R., Gao, H., Fields, S., Shinton, S.A., Medina, K.L., Ikawa, T., Murre, C., Singh, H., Hardy, R.R., et al. (2004). Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription. Nat. Immunol. 5, 1069-1077. https://doi.org/10.1038/ni1119
  25. Mandel, E.M. and Grosschedl, R. (2010). Transcription control of early B cell differentiation. Curr. Opin. Immunol. 22, 161-167. https://doi.org/10.1016/j.coi.2010.01.010
  26. 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). Runx3 programs CD8(+) T cell residency in non-lymphoid tissues and tumours. Nature 552, 253-257. https://doi.org/10.1038/nature24993
  27. Mucida, D., Husain, M.M., Muroi, S., van Wijk, F., Shinnakasu, R., Naoe, Y., Reis, B.S., Huang, Y., Lambolez, F., Docherty, M., et al. (2013). Transcriptional reprogramming of mature CD4(+) helper T cells generates distinct MHC class II-restricted cytotoxic T lymphocytes. Nat. Immunol. 14, 281-289. https://doi.org/10.1038/ni.2523
  28. Mundlos, S., Otto, F., Mundlos, C., Mulliken, J.B., Aylsworth, A.S., Albright, S., Lindhout, D., Cole, W.G., Henn, W., Knoll, J.H., et al. (1997). Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. Cell 89, 773-779. https://doi.org/10.1016/S0092-8674(00)80260-3
  29. Nieke, S., Yasmin, N., Kakugawa, K., Yokomizo, T., Muroi, S., and Taniuchi, I. (2017). Unique N-terminal sequences in two Runx1 isoforms are dispensable for Runx1 function. BMC Dev. Biol. 17, 14. https://doi.org/10.1186/s12861-017-0156-y
  30. O’Sullivan, T.E., Sun, J.C., and Lanier, L.L. (2015). Natural killer cell memory. Immunity 43, 634-645. https://doi.org/10.1016/j.immuni.2015.09.013
  31. Ohno, S., Sato, T., Kohu, K., Takeda, K., Okumura, K., Satake, M., and Habu, S. (2008). Runx proteins are involved in regulation of CD122, Ly49 family and IFN-gamma expression during NK cell differentiation. Int. Immunol. 20, 71-79. https://doi.org/10.1093/intimm/dxm120
  32. Okuda, T., van Deursen, J., Hiebert, S.W., Grosveld, G., and Downing, J.R. (1996). AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell 84, 321-330. https://doi.org/10.1016/S0092-8674(00)80986-1
  33. Ono, M., Yaguchi, H., Ohkura, N., Kitabayashi, I., Nagamura, Y., Nomura, T., Miyachi, Y., Tsukada, T., and Sakaguchi, S. (2007). Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1. Nature 446, 685-689. https://doi.org/10.1038/nature05673
  34. Otto, F., Thornell, A.P., Crompton, T., Denzel, A., Gilmour, K.C., Rosewell, I.R., Stamp, G.W., Beddington, R.S., Mundlos, S., Olsen, B.R., et al. (1997). Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89, 765-771. https://doi.org/10.1016/S0092-8674(00)80259-7
  35. Pardali, E., Xie, X.Q., Tsapogas, P., Itoh, S., Arvanitidis, K., Heldin, C.H., ten Dijke, P., Grundstrom, T., and Sideras, P. (2000). Smad and AML proteins synergistically confer transforming growth factor beta1 responsiveness to human germ-line IgA genes. J. Biol. Chem. 275, 3552-3560. https://doi.org/10.1074/jbc.275.5.3552
  36. Park, J.H., Adoro, S., Guinter, T., Erman, B., Alag, A.S., Catalfamo, M., Kimura, M.Y., Cui, Y., Lucas, P.J., Gress, R.E., et al. (2010). Signaling by intrathymic cytokines, not T cell antigen receptors, specifies CD8 lineage choice and promotes the differentiation of cytotoxic-lineage T cells. Nat. Immunol. 11, 257-264. https://doi.org/10.1038/ni.1840
  37. Pham, D., Vincentz, J.W., Firulli, A.B., and Kaplan, M.H. (2012). Twist1 regulates Ifng expression in Th1 cells by interfering with Runx3 function. J. Immunol. 189, 832-840. https://doi.org/10.4049/jimmunol.1200854
  38. Rapp, M., Lau, C.M., Adams, N.M., Weizman, O.E., O'Sullivan, T.E., Geary, C.D., and Sun, J.C. (2017). Core-binding factor ${\beta}$ and Runx transcription factors promote adaptive natural killer cell responses. Sci. Immunol. 2, eaan3796. https://doi.org/10.1126/sciimmunol.aan3796
  39. Reis, B.S., Rogoz, A., Costa-Pinto, F.A., Taniuchi, I., and Mucida, D. (2013). Mutual expression of the transcription factors Runx3 and ThPOK regulates intestinal CD4(+) T cell immunity. Nat. Immunol. 14, 271-280. https://doi.org/10.1038/ni.2518
  40. Rudra, D., Egawa, T., Chong, M.M., Treuting, P., Littman, D.R., and Rudensky, A.Y. (2009). Runx-CBFbeta complexes control expression of the transcription factor Foxp3 in regulatory T cells. Nat. Immunol. 10, 1170-1177. https://doi.org/10.1038/ni.1795
  41. Sakaguchi, S., Hainberger, D., Tizian, C., Tanaka, H., Okuda, T., Taniuchi, I., and Ellmeier, W. (2015). MAZR and Runx factors synergistically repress ThPOK during CD8+ T cell lineage development. J. Immunol. 195, 2879-2887. https://doi.org/10.4049/jimmunol.1500387
  42. Sakaguchi, S., Hombauer, M., Bilic, I., Naoe, Y., Schebesta, A., Taniuchi, I., and Ellmeier, W. (2010). The zinc-finger protein MAZR is part of the transcription factor network that controls the CD4 versus CD8 lineage fate of double-positive thymocytes. Nat. Immunol. 11, 442-448. https://doi.org/10.1038/ni.1860
  43. Sellars, M., Huh, J.R., Day, K., Issuree, P.D., Galan, C., Gobeil, S., Absher, D., Green, M.R., and Littman, D.R. (2015). Regulation of DNA methylation dictates Cd4 expression during the development of helper and cytotoxic T cell lineages. Nat. Immunol. 16, 746-754. https://doi.org/10.1038/ni.3198
  44. Seo, W., Ikawa, T., Kawamoto, H., and Taniuchi, I. (2012). Runx1-Cbfbeta facilitates early B lymphocyte development by regulating expression of Ebf1. J. Exp. Med. 209, 1255-1262. https://doi.org/10.1084/jem.20112745
  45. Seo, W., Muroi, S., Akiyama, K., and Taniuchi, I. (2017). Distinct requirement of Runx complexes for TCRbeta enhancer activation at distinct developmental stages. Sci. Rep. 7, 41351. https://doi.org/10.1038/srep41351
  46. Setoguchi, R., Tachibana, M., Naoe, Y., Muroi, S., Akiyama, K., Tezuka, C., Okuda, T., and Taniuchi, I. (2008). Repression of the transcription factor Th-POK by Runx complexes in cytotoxic T cell development. Science 319, 822-825. https://doi.org/10.1126/science.1151844
  47. Shi, M.J. and Stavnezer, J. (1998). CBF alpha3 (AML2) is induced by TGFbeta1 to bind and activate the mouse germline Ig alpha promoter. J. Immunol. 161, 6751-6760.
  48. Stavnezer, J. and Kang, J. (2009). The surprising discovery that TGF beta specifically induces the IgA class switch. J. Immunol. 182, 5-7. https://doi.org/10.4049/jimmunol.182.1.5
  49. Sun, G., Liu, X., Mercado, P., Jenkinson, S.R., Kypriotou, M., Feigenbaum, L., Galera, P., and Bosselut, R. (2005). The zinc finger protein cKrox directs CD4 lineage differentiation during intrathymic T cell positive selection. Nat. Immunol. 6, 373-381. https://doi.org/10.1038/ni1183
  50. Sun, J.C., Madera, S., Bezman, N.A., Beilke, J.N., Kaplan, M.H., and Lanier, L.L. (2012). Proinflammatory cytokine signaling required for the generation of natural killer cell memory. J. Exp. Med. 209, 947-954. https://doi.org/10.1084/jem.20111760
  51. Taniuchi, I., Osato, M., Egawa, T., Sunshine, M.J., Bae, S.C., Komori, T., Ito, Y., and Littman, D.R. (2002). Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development. Cell 111, 621-633. https://doi.org/10.1016/S0092-8674(02)01111-X
  52. Tenno, M., Kojo, S., Lawir, D.F., Hess, I., Shiroguchi, K., Ebihara, T., Endo, T.A., Muroi, S., Satoh, R., Kawamoto, H., et al. (2018). Cbfbeta2 controls differentiation of and confers homing capacity to prethymic progenitors. J. Exp. Med. 215, 595-610. https://doi.org/10.1084/jem.20171221
  53. Tenno, M., Shiroguchi, K., Muroi, S., Kawakami, E., Koseki, K., Kryukov, K., Imanishi, T., Ginhoux, F., and Taniuchi, I. (2017). Cbfbeta2 deficiency preserves Langerhans cell precursors by lack of selective TGFbeta receptor signaling. J. Exp. Med. 214, 2933-2946. https://doi.org/10.1084/jem.20170729
  54. Thapa, P., Manso, B., Chung, J.Y., Romera Arocha, S., Xue, H.H., Angelo, D.B.S., and Shapiro, V.S. (2017). The differentiation of ROR-gammat expressing iNKT17 cells is orchestrated by Runx1. Sci. Rep. 7, 7018. https://doi.org/10.1038/s41598-017-07365-8
  55. Tsagaratou, A., Aijo, T., Lio, C.W., Yue, X., Huang, Y., Jacobsen, S.E., Lahdesmaki, H., and Rao, A. (2014). Dissecting the dynamic changes of 5-hydroxymethylcytosine in T-cell development and differentiation. Proc. Natl. Acad. Sci. U. S. A. 111, E3306-E3315. https://doi.org/10.1073/pnas.1412327111
  56. Vivier, E., Raulet, D.H., Moretta, A., Caligiuri, M.A., Zitvogel, L., Lanier, L.L., Yokoyama, W.M., and Ugolini, S. (2011). Innate or adaptive immunity? The example of natural killer cells. Science 331, 44-49. https://doi.org/10.1126/science.1198687
  57. Wang, D., Diao, H., Getzler, A.J., Rogal, W., Frederick, M.A., Milner, J., Yu, B., Crotty, S., Goldrath, A.W., and Pipkin, M.E. (2018). The transcription factor Runx3 establishes chromatin accessibility of cis-regulatory landscapes that drive memory cytotoxic t lymphocyte formation. Immunity 48, 659-674.e6. https://doi.org/10.1016/j.immuni.2018.03.028
  58. Wang, Q., Stacy, T., Binder, M., Marin-Padilla, M., Sharpe, A.H., and Speck, N.A. (1996a). Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. Proc. Natl. Acad. Sci. U. S. A. 93, 3444-3449. https://doi.org/10.1073/pnas.93.8.3444
  59. Wang, Q., Stacy, T., Miller, J.D., Lewis, A.F., Gu, T.L., Huang, X., Bushweller, J.H., Bories, J.C., Alt, F.W., Ryan, G., et al. (1996b). The CBFbeta subunit is essential for CBFalpha2 (AML1) function in vivo. Cell 87, 697-708. https://doi.org/10.1016/S0092-8674(00)81389-6
  60. Wang, Y., Godec, J., Ben-Aissa, K., Cui, K., Zhao, K., Pucsek, A.B., Lee, Y.K., Weaver, C.T., Yagi, R., and Lazarevic, V. (2014). The transcription factors T-bet and Runx are required for the ontogeny of pathogenic interferongamma-producing T helper 17 cells. Immunity 40, 355-366. https://doi.org/10.1016/j.immuni.2014.01.002
  61. Watanabe, K., Sugai, M., Nambu, Y., Osato, M., Hayashi, T., Kawaguchi, M., Komori, T., Ito, Y., and Shimizu, A. (2010). Requirement for Runx proteins in IgA class switching acting downstream of TGF-beta 1 and retinoic acid signaling. J. Immunol. 184, 2785-2792. https://doi.org/10.4049/jimmunol.0901823
  62. Woolf, E., Brenner, O., Goldenberg, D., Levanon, D., and Groner, Y. (2007). Runx3 regulates dendritic epidermal T cell development. Dev. Biol. 303, 703-714. https://doi.org/10.1016/j.ydbio.2006.12.005
  63. Xing, S., Shao, P., Li, F., Zhao, X., Seo, W., Wheat, J.C., Ramasamy, S., Wang, J., Li, X., Peng, W., et al. (2018). Tle corepressors are differentially partitioned to instruct CD8(+) T cell lineage choice and identity. J. Exp. Med. 215, 2211-2226. https://doi.org/10.1084/jem.20171514
  64. Zeidan, N., Damen, H., Roy, D.C., and Dave, V.P. (2019). Critical role for TCR signal strength and MHC specificity in ThPOK-Induced CD4 helper lineage choice. J. Immunol. 202, 3211-3225. https://doi.org/10.4049/jimmunol.1801464
  65. Zhang, F., Meng, G., and Strober, W. (2008). Interactions among the transcription factors Runx1, RORgammat and Foxp3 regulate the differentiation of interleukin 17-producing T cells. Nat. Immunol. 9, 1297-1306. https://doi.org/10.1038/ni.1663
  66. Zhang, Y. and Derynck, R. (2000). Transcriptional regulation of the transforming growth factor-beta-inducible mouse germ line Ig alpha constant region gene by functional cooperation of Smad, CREB, and AML family members. J. Biol. Chem. 275, 16979-16985. https://doi.org/10.1074/jbc.M001526200
  67. Zhao, X., Jankovic, V., Gural, A., Huang, G., Pardanani, A., Menendez, S., Zhang, J., Dunne, R., Xiao, A., Erdjument-Bromage, H., et al. (2008). Methylation of RUNX1 by PRMT1 abrogates SIN3A binding and potentiates its transcriptional activity. Genes Dev. 22, 640-653. https://doi.org/10.1101/gad.1632608
  68. Zheng, Y., Josefowicz, S., Chaudhry, A., Peng, X.P., Forbush, K., and Rudensky, A.Y. (2010). Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 463, 808-812. https://doi.org/10.1038/nature08750

Cited by

  1. Runx Transcription Factors in T Cells-What Is Beyond Thymic Development? vol.12, 2020, https://doi.org/10.3389/fimmu.2021.701924
  2. IPEX Syndrome: Genetics and Treatment Options vol.12, pp.3, 2020, https://doi.org/10.3390/genes12030323
  3. Runx1 shapes the chromatin landscape via a cascade of direct and indirect targets vol.17, pp.6, 2020, https://doi.org/10.1371/journal.pgen.1009574
  4. The Multiple Interactions of RUNX with the Hippo-YAP Pathway vol.10, pp.11, 2020, https://doi.org/10.3390/cells10112925
  5. Expression patterns and prognostic value of RUNX genes in kidney cancer vol.11, pp.1, 2020, https://doi.org/10.1038/s41598-021-94294-2
  6. RUNX1 Regulates a Transcription Program That Affects the Dynamics of Cell Cycle Entry of Naive Resting B Cells vol.207, pp.12, 2021, https://doi.org/10.4049/jimmunol.2001367