The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through super-enhancers to drive chondrogenesis

Nucleic Acids Research

Volumn 43, Issue 17, 2015, Pages 8183-8203

  Liu, Chia Feng ^a   Lefebvre, Véronique ^a  

^a LERNER RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FIBROBLAST GROWTH FACTOR RECEPTOR 3; TRANSCRIPTION FACTOR RUNX2; TRANSCRIPTION FACTOR RUNX3; TRANSCRIPTION FACTOR SOX5; TRANSCRIPTION FACTOR SOX6; TRANSCRIPTION FACTOR SOX9; TRANSCRIPTION FACTOR SOX;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CARTILAGE CELL; CELL DIFFERENTIATION; CELL LINE; CELL PROLIFERATION; CELL SPECIFICITY; CHONDROGENESIS; CHST11 GENE; CONTROLLED STUDY; EMBRYO; ENHANCER REGION; EXTRACELLULAR MATRIX; FEMALE; FGFR3 GENE; GENE; GENE EXPRESSION; GENE IDENTIFICATION; GENE TARGETING; GENOME; GROWTH PLATE; HYPERTROPHY; IN VIVO STUDY; NEWBORN; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN MOTIF; RAT; RCS CELL LINE; REGULATORY MECHANISM; RUNX2 GENE; RUNX3 GENE; ANIMAL; CHLOROCEBUS AETHIOPS; CHONDROCYTE; COS CELL LINE; CYTOLOGY; EPIPHYSIS PLATE; GENETICS; HEK293 CELL LINE; HUMAN; METABOLISM; MOUSE; TUMOR CELL LINE;

ANIMALS; CELL LINE, TUMOR; CELL PROLIFERATION; CERCOPITHECUS AETHIOPS; CHONDROCYTES; CHONDROGENESIS; COS CELLS; ENHANCER ELEMENTS, GENETIC; FEMALE; GENE EXPRESSION; GENOME; GROWTH PLATE; HEK293 CELLS; HUMANS; MICE; RATS; SOX9 TRANSCRIPTION FACTOR; SOXD TRANSCRIPTION FACTORS;

EID: 84946502746     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gkv688     Document Type: Article

References (91)

1. Kobayashi, T. and Kronenberg, H.M. (2014) Overview of skeletal development. Methods Mol. Biol., 1130, 3-12.
2. Kozhemyakina, E., Lassar, A.B. and Zelzer, E. (2015) A pathway to bone: signaling molecules and transcription factors involved in chondrocyte development and maturation. Development, 142, 817-831.
3. Long, F. and Ornitz, D.M. (2013) Development of the endochondral skeleton. Cold Spring Harb. Perspect. Biol., 5, a008334.
4. Warman, M.L., Cormier-Daire, V., Hall, C., Krakow, D., Lachman, R., LeMerrer, M., Mortier, G., Mundlos, S., Nishimura, G., Rimoin, D.L. et al. (2011) Nosology and classification of genetic skeletal disorders: 2010 revision. Am. J. Med. Genet. A, 155, 943-968.
5. Musumeci, G., Aiello, F.C., Szychlinska, M.A., Di Rosa, M., Castrogiovanni, P. and Mobasheri, A. (2015) Osteoarthritis in the XXIst century: risk factors and behaviours that influence disease onset and progression. Int. J. Mol. Sci., 16, 6093-6112.
6. Lefebvre, V., Li, P. and de Crombrugghe, B. (1998) A new long form of Sox5 (L-Sox5), Sox6 and Sox9 are coexpressed in chondrogenesis and cooperatively activate the type II collagen gene. EMBO J., 17, 5718-5733.
7. Hiraoka, Y., Ogawa, M., Sakai, Y., Kido, S. and Aiso, S. (1998) The mouse Sox5 gene encodes a protein containing the leucine zipper and the Q box. Biochim. Biophys. Acta, 1399, 40-46.
8. Kamachi, Y. and Kondoh, H. (2013) Sox proteins: regulators of cell fate specification and differentiation. Development, 140, 4129-4144.
9. Lefebvre, V. (2010) The SoxD transcription factors-Sox5, Sox6, and Sox13-are key cell fate modulators. Int. J. Biochem. Cell. Biol., 42, 429-432.
10. Akiyama, H. and Lefebvre, V. (2011) Unraveling the transcriptional regulatory machinery in chondrogenesis. J. Bone Miner. Metab., 29, 390-395.
11. Zhao, Q., Eberspaecher, H., Lefebvre, V. and De Crombrugghe, B. (1997) Parallel expression of Sox9 and Col2a1 in cells undergoing chondrogenesis. Dev. Dyn., 209, 377-386.
12. Ng, L.J., Wheatley, S., Muscat, G.E., Conway-Campbell, J., Bowles, J., Wright, E., Bell, D.M., Tam, P.P., Cheah, K.S. and Koopman, P. (1997) SOX9 binds DNA, activates transcription, and coexpresses with type II collagen during chondrogenesis in the mouse. Dev. Biol., 183, 108-121.
13. Wagner, T., Wirth, J., Meyer, J., Zabel, B., Held, M., Zimmer, J., Pasantes, J., Bricarelli, F.D., Keutel, J., Hustert, E. et al. (1994) Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell, 79, 1111-1120.
14. Foster, J.W., Dominguez-Steglich, M.A., Guioli, S., Kwok, C., Weller, P.A., Stevanovic, M., Weissenbach, J., Mansour, S., Young, I.D., Goodfellow, P.N. et al. (1994) Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene. Nature, 372, 525-530.
15. Akiyama, H., Chaboissier, M.C., Martin, J.F., Schedl, A. and de Crombrugghe, B. (2002) The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6. Genes Dev., 16, 2813-2828.
16. Henry, S.P., Liang, S., Akdemir, K.C. and de Crombrugghe, B. (2012) The postnatal role of Sox9 in cartilage. J. Bone Miner. Res., 27, 2511-2525.
17. Dy, P., Wang, W., Bhattaram, P., Wang, Q., Wang, L., Ballock, R.T. and Lefebvre, V. (2012) Sox9 directs hypertrophic maturation and blocks osteoblast differentiation of growth plate chondrocytes. Dev. Cell, 22, 597-609.
18. Smits, P., Dy, P., Mitra, S. and Lefebvre, V. (2004) Sox5 and Sox6 are needed to develop and maintain source, columnar, and hypertrophic chondrocytes in the cartilage growth plate. J. Cell Biol., 164, 747-758.
19. Smits, P., Li, P., Mandel, J., Zhang, Z., Deng, J.M., Behringer, R.R., de Crombrugghe, B. and Lefebvre, V. (2001) The transcription factors L-Sox5 and Sox6 are essential for cartilage formation. Dev. Cell, 1, 277-290.
20. Dy, P., Smits, P., Silvester, A., Penzo-Mendez, A., Dumitriu, B., Han, Y., de la Motte, C.A., Kingsley, D.M. and Lefebvre, V. (2010) Synovial joint morphogenesis requires the chondrogenic action of Sox5 and Sox6 in growth plate and articular cartilage. Dev. Biol., 341, 346-359.
21. Han, Y. and Lefebvre, V. (2008) L-Sox5 and Sox6 drive expression of the aggrecan gene in cartilage by securing binding of Sox9 to a far-upstream enhancer. Mol. Cell. Biol., 28, 4999-5013.
22. Oh, C.D., Lu, Y., Liang, S., Mori-Akiyama, Y., Chen, D., de Crombrugghe, B. and Yasuda, H. (2014) SOX9 regulates multiple genes in chondrocytes, including genes encoding ECM proteins, ECM modification enzymes, receptors, and transporters. PLoS One, 9, e107577.
23. Oh, C.D., Maity, S.N., Lu, J.F., Zhang, J., Liang, S., Coustry, F., de Crombrugghe, B. and Yasuda, H. (2010) Identification of SOX9 interaction sites in the genome of chondrocytes. PLoS One, 5, e10113.
24. Leung, V.Y., Gao, B., Leung, K.K., Melhado, I.G., Wynn, S.L., Au, T.Y., Dung, N.W., Lau, J.Y., Mak, A.C., Chan, D. et al. (2011) SOX9 governs differentiation stage-specific gene expression in growth plate chondrocytes via direct concomitant transactivation and repression. PLoS Genet., 7, e1002356.
25. Stolt, C.C., Lommes, P., Hillgartner, S. and Wegner, M. (2008) The transcription factor Sox5 modulates Sox10 function during melanocyte development. Nucleic Acids Res., 36, 5427-5440.
26. Stolt, C.C., Schlierf, A., Lommes, P., Hillgartner, S., Werner, T., Kosian, T., Sock, E., Kessaris, N., Richardson, W.D., Lefebvre, V. et al. (2006) SoxD proteins influence multiple stages of oligodendrocyte development and modulate SoxE protein function. Dev. Cell, 11, 697-709.
27. Yi, Z., Cohen-Barak, O., Hagiwara, N., Kingsley, P.D., Fuchs, D.A., Erickson, D.T., Epner, E.M., Palis, J. and Brilliant, M.H. (2006) Sox6 directly silences epsilon globin expression in definitive erythropoiesis. PLoS Genet., 2, e14.
28. An, C.I., Dong, Y. and Hagiwara, N. (2011) Genome-wide mapping of Sox6 binding sites in skeletal muscle reveals both direct and indirect regulation of muscle terminal differentiation by Sox6. BMC Dev. Biol., 11, 59.
29. Quiat, D., Voelker, K.A., Pei, J., Grishin, N.V., Grange, R.W., Bassel-Duby, R. and Olson, E.N. (2011) Concerted regulation of myofiber-specific gene expression and muscle performance by the transcriptional repressor Sox6. Proc. Natl. Acad. Sci. U.S.A., 108, 10196-10201.
30. Adam, R.C., Yang, H., Rockowitz, S., Larsen, S.B., Nikolova, M., Oristian, D.S., Polak, L., Kadaja, M., Asare, A., Zheng, D. et al. (2015) Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice. Nature, 521, 366-370.
31. Whyte, W.A., Orlando, D.A., Hnisz, D., Abraham, B.J., Lin, C.Y., Kagey, M.H., Rahl, P.B., Lee, T.I. and Young, R.A. (2013) Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell, 153, 307-319.
32. Hnisz, D., Abraham, B.J., Lee, T.I., Lau, A., Saint-Andre, V., Sigova, A.A., Hoke, H.A. and Young, R.A. (2013) Super-enhancers in the control of cell identity and disease. Cell, 155, 934-947.
33. King, K.B. and Kimura, J.H. (2003) The establishment and characterization of an immortal cell line with a stable chondrocytic phenotype. J. Cell. Biochem., 89, 992-1004.
34. Dy, P., Han, Y. and Lefebvre, V. (2008) Generation of mice harboring a Sox5 conditional null allele. Genesis, 46, 294-299.
35. Dumitriu, B., Dy, P., Smits, P. and Lefebvre, V. (2006) Generation of mice harboring a Sox6 conditional null allele. Genesis, 44, 219-224.
36. Kist, R., Schrewe, H., Balling, R. and Scherer, G. (2002) Conditional inactivation of Sox9: a mouse model for campomelic dysplasia. Genesis, 32, 121-123.
37. Logan, M., Martin, J.F., Nagy, A., Lobe, C., Olson, E.N. and Tabin, C.J. (2002) Expression of Cre Recombinase in the developing mouse limb bud driven by a Prxl enhancer. Genesis, 33, 77-80.
38. Anders, S. and Huber, W. (2010) Differential expression analysis for sequence count data. Genome Biol., 11, R106.
39. Park, J.S., Ma, W., O'Brien, L.L., Chung, E., Guo, J.J., Cheng, J.G., Valerius, M.T., McMahon, J.A., Wong, W.H. and McMahon, A.P. (2012) Six2 and Wnt regulate self-renewal and commitment of nephron progenitors through shared gene regulatory networks. Dev. Cell, 23, 637-651.
40. Feng, J., Liu, T., Qin, B., Zhang, Y. and Liu, X.S. (2012) Identifying ChIP-seq enrichment using MACS. Nat. Protoc., 7, 1728-1740.
41. Huang, W., Loganantharaj, R., Schroeder, B., Fargo, D. and Li, L. (2013) PAVIS: a tool for peak annotation and visualization. Bioinformatics, 29, 3097-3099.
42. Bailey, T.L., Boden, M., Buske, F.A., Frith, M., Grant, C.E., Clementi, L., Ren, J., Li, W.W. and Noble, W.S. (2009) MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res., 37, W202-W208.
43. Bailey, T.L. and Machanick, P. (2012) Inferring direct DNA binding from ChIP-seq. Nucleic Acids Res., 40, e128.
44. McLeay, R.C. and Bailey, T.L. (2010) Motif Enrichment Analysis: a unified framework and an evaluation on ChIP data. BMC Bioinformatics, 11, 165.
45. Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y.C., Laslo, P., Cheng, J.X., Murre, C., Singh, H. and Glass, C.K. (2010) Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell, 38, 576-589.
46. Bhattaram, P., Penzo-Mendez, A., Kato, K., Bandyopadhyay, K., Gadi, A., Taketo, M.M. and Lefebvre, V. (2014) SOXC proteins amplify canonical WNT signaling to secure nonchondrocytic fates in skeletogenesis. J. Cell Biol., 207, 657-671.
47. Ducy, P., Zhang, R., Geoffroy, V., Ridall, A.L. and Karsenty, G. (1997) Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell, 89, 747-754.
48. Lefebvre, V., Zhou, G., Mukhopadhyay, K., Smith, C.N., Zhang, Z., Eberspaecher, H., Zhou, X., Sinha, S., Maity, S.N. and de Crombrugghe, B. (1996) An 18-base-pair sequence in the mouse proalpha1(II) collagen gene is sufficient for expression in cartilage and binds nuclear proteins that are selectively expressed in chondrocytes. Mol. Cell. Biol., 16, 4512-4523.
49. Yao, B., Wang, Q., Liu, C.F., Bhattaram, P., Li, W., Mead, T.J., Crish, J.F. and Lefebvre, V. (2015) The SOX9 upstream region prone to chromosomal aberrations causing campomelic dysplasia contains multiple cartilage enhancers. Nucleic Acids Res., 43, 5394-5408.
50. Mukhopadhyay, K., Lefebvre, V., Zhou, G., Garofalo, S., Kimura, J.H. and de Crombrugghe, B. (1995) Use of a new rat chondrosarcoma cell line to delineate a 119-base pair chondrocyte-specific enhancer element and to define active promoter segments in the mouse pro-alpha 1(II) collagen gene. J. Biol. Chem., 270, 27711-27719.
51. Shinomura, T., Ito, K., Hook, M. and Kimura, J.H. (2012) A newly identified enhancer element responsible for type II collagen gene expression. J. Biochem., 152, 565-575.
52. Bosserhoff, A.K., Kondo, S., Moser, M., Dietz, U.H., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Buettner, R. and Sandell, L.J. (1997) Mouse CD-RAP/MIA gene: structure, chromosomal localization, and expression in cartilage and chondrosarcoma. Dev. Dyn., 208, 516-525.
53. Fernandes, R.J., Schmid, T.M., Harkey, M.A. and Eyre, D.R. (1997) Incomplete processing of type II procollagen by a rat chondrosarcoma cell line. Eur. J. Biochem., 247, 620-624.
54. Zou, W., Chen, X., Shim, J.H., Huang, Z., Brady, N., Hu, D., Drapp, R., Sigrist, K., Glimcher, L.H. and Jones, D. (2011) The E3 ubiquitin ligase Wwp2 regulates craniofacial development through mono-ubiquitylation of Goosecoid. Nat. Cell Biol., 13, 59-65.
55. Nakamura, Y., Yamamoto, K., He, X., Otsuki, B., Kim, Y., Murao, H., Soeda, T., Tsumaki, N., Deng, J.M., Zhang, Z. et al. (2011) Wwp2 is essential for palatogenesis mediated by the interaction between Sox9 and mediator subunit 25. Nat. Commun., 2, 251.
56. Sock, E., Pagon, R.A., Keymolen, K., Lissens, W., Wegner, M. and Scherer, G. (2003) Loss of DNA-dependent dimerization of the transcription factor SOX9 as a cause for campomelic dysplasia. Hum. Mol. Genet., 12, 1439-1447.
57. Bridgewater, L.C., Walker, M.D., Miller, G.C., Ellison, T.A., Holsinger, L.D., Potter, J.L., Jackson, T.L., Chen, R.K., Winkel, V.L., Zhang, Z. et al. (2003) Adjacent DNA sequences modulate Sox9 transcriptional activation at paired Sox sites in three chondrocyte-specific enhancer elements. Nucleic Acids Res., 31, 1541-1553.
58. Kluppel, M., Wight, T.N., Chan, C., Hinek, A. and Wrana, J.L. (2005) Maintenance of chondroitin sulfation balance by chondroitin-4-sulfotransferase 1 is required for chondrocyte development and growth factor signaling during cartilage morphogenesis. Development, 132, 3989-4003.
59. Hu, G., Codina, M. and Fisher, S. (2012) Multiple enhancers associated with ACAN suggest highly redundant transcriptional regulation in cartilage. Matrix Biol., 31, 328-337.
60. Mead, T.J., Wang, Q., Bhattaram, P., Dy, P., Afelik, S., Jensen, J. and Lefebvre, V. (2013) A far-upstream (-70 kb) enhancer mediates Sox9 auto-regulation in somatic tissues during development and adult regeneration. Nucleic Acids Res., 41, 4459-4469.
61. Kumar, D. and Lassar, A.B. (2009) The transcriptional activity of Sox9 in chondrocytes is regulated by RhoA signaling and actin polymerization. Mol. Cell. Biol., 29, 4262-4273.
62. Zeng, L., Kempf, H., Murtaugh, L.C., Sato, M.E. and Lassar, A.B. (2002) Shh establishes an Nkx3.2/Sox9 autoregulatory loop that is maintained by BMP signals to induce somitic chondrogenesis. Genes Dev., 16, 1990-2005.
63. Yamashita, S., Andoh, M., Ueno-Kudoh, H., Sato, T., Miyaki, S. and Asahara, H. (2009) Sox9 directly promotes Bapx1 gene expression to repress Runx2 in chondrocytes. Exp. Cell Res., 315, 2231-2240.
64. Amano, K., Hata, K., Muramatsu, S., Wakabayashi, M., Takigawa, Y., Ono, K., Nakanishi, M., Takashima, R., Kogo, M., Matsuda, A. et al. (2011) Arid5a cooperates with Sox9 to stimulate chondrocyte-specific transcription. Mol. Biol. Cell, 22, 1300-1311.
65. Miyaki, S., Sato, T., Inoue, A., Otsuki, S., Ito, Y., Yokoyama, S., Kato, Y., Takemoto, F., Nakasa, T., Yamashita, S. et al. (2010) MicroRNA-140 plays dual roles in both cartilage development and homeostasis. Genes Dev., 24, 1173-1185.
66. Kadaja, M., Keyes, B.E., Lin, M., Pasolli, H.A., Genander, M., Polak, L., Stokes, N., Zheng, D. and Fuchs, E. (2014) SOX9: a stem cell transcriptional regulator of secreted niche signaling factors. Genes Dev., 28, 328-341.
67. Nakamura, Y., He, X., Kato, H., Wakitani, S., Kobayashi, T., Watanabe, S., Iida, A., Tahara, H., Warman, M.L., Watanapokasin, R. et al. (2012) Sox9 is upstream of microRNA-140 in cartilage. Appl. Biochem. Biotechnol., 166, 64-71.
68. Tuddenham, L., Wheeler, G., Ntounia-Fousara, S., Waters, J., Hajihosseini, M.K., Clark, I. and Dalmay, T. (2006) The cartilage specific microRNA-140 targets histone deacetylase 4 in mouse cells. FEBS Lett., 580, 4214-4217.
69. Rozenblatt-Rosen, O., Mosonego-Ornan, E., Sadot, E., Madar-Shapiro, L., Sheinin, Y., Ginsberg, D. and Yayon, A. (2002) Induction of chondrocyte growth arrest by FGF: transcriptional and cytoskeletal alterations. J. Cell Sci., 115, 553-562.
70. Yao, R., Natsume, Y. and Noda, T. (2007) TACC3 is required for the proper mitosis of sclerotome mesenchymal cells during formation of the axial skeleton. Cancer Sci., 98, 555-562.
71. Yoshida, C.A., Yamamoto, H., Fujita, T., Furuichi, T., Ito, K., Inoue, K., Yamana, K., Zanma, A., Takada, K., Ito, Y. et al. (2004) Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog. Genes Dev., 18, 952-963.
72. Storm, E.E. and Kingsley, D.M. (1999) GDF5 coordinates bone and joint formation during digit development. Dev. Biol., 209, 11-27.
73. Settle, S.H. Jr, Rountree, R.B., Sinha, A., Thacker, A., Higgins, K. and Kingsley, D.M. (2003) Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes. Dev. Biol., 254, 116-130.
74. Rhee, D.K., Marcelino, J., Baker, M., Gong, Y., Smits, P., Lefebvre, V., Jay, G.D., Stewart, M., Wang, H., Warman, M.L. et al. (2005) The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth. J. Clin. Invest., 115, 622-631.
75. Stevens, J.W., Patil, S.R., Jordan, D.K., Kimura, J.H. and Morcuende, J.A. (2005) Cytogenetics of swarm rat chondrosarcoma. Iowa Orthop. J., 25, 135-140.
76. Bi, W., Deng, J.M., Zhang, Z., Behringer, R.R. and de Crombrugghe, B. (1999) Sox9 is required for cartilage formation. Nat. Genet., 22, 85-89.
77. Szenasi, T., Kenesi, E., Nagy, A., Molnar, A., Balint, B.L., Zvara, A., Csabai, Z., Deak, F., Boros Olah, B., Mates, L. et al. (2013) Hmgb1 can facilitate activation of the matrilin-1 gene promoter by Sox9 and L-Sox5/Sox6 in early steps of chondrogenesis. Biochim. Biophys. Acta, 1829, 1075-1091.
78. Yamashita, S., Miyaki, S., Kato, Y., Yokoyama, S., Sato, T., Barrionuevo, F., Akiyama, H., Scherer, G., Takada, S. and Asahara, H. (2012) L-Sox5 and Sox6 proteins enhance chondrogenic miR-140 microRNA expression by strengthening dimeric Sox9 activity. J. Biol. Chem., 287, 22206-22215.
79. Kondoh, H. and Kamachi, Y. (2010) SOX-partner code for cell specification: Regulatory target selection and underlying molecular mechanisms. Int. J. Biochem. Cell Biol., 42, 391-399.
80. Chen, X., Xu, H., Yuan, P., Fang, F., Huss, M., Vega, V.B., Wong, E., Orlov, Y.L., Zhang, W., Jiang, J. et al. (2008) Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell, 133, 1106-1117.
81. Kuo, P.Y., Leshchenko, V.V., Fazzari, M.J., Perumal, D., Gellen, T., He, T., Iqbal, J., Baumgartner-Wennerholm, S., Nygren, L., Zhang, F. et al. (2014) High-resolution chromatin immunoprecipitation (ChIP) sequencing reveals novel binding targets and prognostic role for SOX11 in mantle cell lymphoma. Oncogene, 34, 1231-1240.
82. Zaret, K.S., Watts, J., Xu, J., Wandzioch, E., Smale, S.T. and Sekiya, T. (2008) Pioneer factors, genetic competence, and inductive signaling: programming liver and pancreas progenitors from the endoderm. Cold Spring Harb. Symp. Quant. Biol., 73, 119-126.
83. Cuesta, I., Zaret, K.S. and Santisteban, P. (2007) The forkhead factor FoxE1 binds to the thyroperoxidase promoter during thyroid cell differentiation and modifies compacted chromatin structure. Mol. Cell. Biol., 27, 7302-7314.
84. Kume, T., Deng, K.Y., Winfrey, V., Gould, D.B., Walter, M.A. and Hogan, B.L. (1998) The forkhead/winged helix gene Mf1 is disrupted in the pleiotropic mouse mutation congenital hydrocephalus. Cell, 93, 985-996.
85. Inman, K.E., Purcell, P., Kume, T. and Trainor, P.A. (2013) Interaction between Foxc1 and Fgf8 during mammalian jaw patterning and in the pathogenesis of syngnathia. PLoS Genet., 9, e1003949.
86. Kume, T., Jiang, H., Topczewska, J.M. and Hogan, B.L. (2001) The murine winged helix transcription factors, Foxc1 and Foxc2, are both required for cardiovascular development and somitogenesis. Genes Dev., 15, 2470-2482.
87. Yoshida, M., Hata, K., Takashima, R., Ono, K., Nakamura, E., Takahata, Y., Murakami, T., Iseki, S., Takano-Yamamoto, T., Nishimura, R. et al. (2015) The transcription factor Foxc1 is necessary for Ihh-Gli2-regulated endochondral ossification. Nat. Commun., 6, 6653.
88. Zhou, G., Zheng, Q., Engin, F., Munivez, E., Chen, Y., Sebald, E., Krakow, D. and Lee, B. (2006) Dominance of SOX9 function over RUNX2 during skeletogenesis. Proc. Natl. Acad. Sci. U.S.A., 103, 19004-19009.
89. Zhou, Z.Q., Ota, S., Deng, C., Akiyama, H. and Hurlin, P.J. (2014) Mutant activated FGFR3 impairs endochondral bone growth by preventing SOX9 downregulation in differentiating chondrocytes. Hum. Mol. Genet., 24, 1764-1773.
90. Murakami, S., Balmes, G., McKinney, S., Zhang, Z., Givol, D. and de Crombrugghe, B. (2004) Constitutive activation of MEK1 in chondrocytes causes Stat1-independent achondroplasia-like dwarfism and rescues the Fgfr3-deficient mouse phenotype. Genes Dev., 18, 290-305.
91. Gordon, C.T., Tan, T.Y., Benko, S., Fitzpatrick, D., Lyonnet, S. and Farlie, P.G. (2009) Long-range regulation at the SOX9 locus in development and disease. J. Med. Genet., 46, 649-656.