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Literature Evidence of Autoregulation


Table. Known autoregulation in mammalian transcription factors.

Factor Symbol First Author Year Species Tissue
P53 TP53 Benoit 2000 Human Adenocarcinoma
CEBPA CEBPA Christy 1991 Mouse Adipocytes
CRY1 CRY1 Kume 1999 Mouse Adipocytes
LXRA NR1H3 Ulven 2004 Mouse Adipose
BCL6 BCL6 Wang 2002 Human B-cells
C-MYC MYC Martinotti 1988 Human B-cells
PU.1 SPI1 Okuno 2005 Mouse Bone Marrow
NKX2.5 NKX2-5 Oka 1997 Mouse Cardiocytes
EGR1 EGR1 Saadane 2000 Mouse Cardiocytes
c-jun JUN Angel 1988 Human Cell lines
p50 NFKB1 Ten 1992 Human Cell lines
p50 NFKB1 Cogswell 1993 Human Cell lines
P53 TP53 Hudson 1995 Human Cell lines
RB1 RB1 Ohtani-Fujita 1994 Human Cell lines
CREM CREM Molina 1993 Rat Cell lines
CDX1 CDX1 Beland 2004 Mouse Embryonic carcinoma
GSC GSC Danilov 1998 Mouse Embryonic carcinoma
RB1 RB1 Hamel 1992 Mouse Embryonic carcinoma
c-Fos FOS Sassone-Corsi 1988 Mouse Embryonic Fibroblasts
c-Fos FOS Konig 1989 Mouse Embryonic Fibroblasts
MYOD1 MYOD1 Thayer 1989 Mouse Embryonic Fibroblasts
P53 TP53 Deffie 1993 Mouse Embryonic Fibroblasts
SRF SRF Spencer 1996 Mouse Embryonic Fibroblasts
E2F2 E2F2 Sears 1997 Rat Embryonic Fibroblasts
STRA13 STRA13 Sun 2000 Mouse Embryonic Fibroblasts
RBL1 RBL1 Zhu 1995 Human Embryonic Kidney
xVENT2B xVENT2B Henningfeld 2002 Xenopus Embryos
PIT1 POU1F1 Chen 1990 Mouse Epithelial
HDAC1 HDAC1 Schuettengruber 2003 Mouse Fibroblasts
OCT1 POU2F1 Pankratova 2003 Mouse Fibroblasts
N-Myc MYCN Facchini 1997 Rat Fibroblasts
MYB MYB Nicolaides 1991 Hampster Fibroblasts
PURA PURA Muralidharan 2001 Human Glial/other
C-MYC MYC Kitaura 1991 Human HeLa
ER ESR1 Castles 1997 Human HeLa
ETS1 ETS1 Jorcyk 1991 Human HeLa
junD JUND Berger 1994 Human HeLa
junD JUND Berger 1998 Human HeLa
p49/p100 NFKB2 Lombardi 1995 Human HeLa
MITF-M MITF Saito 2002 Human HeLa
GATA2 GATA2 Grass 2003 Mouse Hematopoeitic
GATA1 GATA1 Nishikawa 2003 Zebrafish Hematopoeitic
CEBPA CEBPA Foka 2001 Human Hepatoma
CEBPB CEBPB Niehof 2001 Human Hepatoma
KLF4 KLF4 Mahatan 1999 Monkey Kidney
CEBPA CEBPA Timchenko 1995 Human Liver
LXRA NR1H3 Li 2002 Human Liver
FOXA2 FOXA2 Pani 1992 Mouse Liver
HNF4A HNF4A Briancon 2004 Mouse Liver
CEBPA CEBPA Legraverend 1993 Rat Liver
TR THRA Sadow 2003 Mouse Liver/Heart
ETS1 ETS1 Oka 1991 Human Lymphocyte
GFI1 GFI1 Doan 2004 Human Lymphocyte
LXRA NR1H3 Lafitte 2001 Human Lymphocyte
LXRa NR1H3 Laffitte 2001 Human Macrophage
OCT4 POU5F1 Okura-Nakanishi 2005 Mouse mES
SOX2 SOX2 Catena 2004 Mouse mES
MYOD MYOD Tapscott 1991 Mouse Muscle
PU.1 SPI1 Chen 1995 Human Myeloid
HES1 HES1 Hirata 2002 Mouse Myoblasts/Fibroblasts/Neuroblastoma/others
N-Myc MYCN Sivak 1997 Human Neuroblastoma
BRN3A POU4F1 Trieu 2003 Mouse Neurons
PAX6 PAX6 Yamaguchi 1997 Human Ocular
PAX6 PAX6 Aota 2003 Mouse Ocular
RUNX2 RUNX2 Tou 2003 Mouse Osteoblasts
RUNX2 RUNX2 Drissi 2000 Mouse Osteoblasts
E2F1 E2F1 Neuman 1994 Human Osteogenic Sarcoma
RB1 RB1 Shan 1994 Human Osteogenic Sarcoma
CDX2 CDX2 Xu 1999 Mouse Pancreas
PIT1 POU1F1 Theill 1993 Rat Pituitary
CREB CREB1 Meyer 1993 Human Placental cells
AR AR Grad 1999 Human Prostate
c-jun JUN Mechta 1994 Human Review
PITX1 PITX1 Goodyer 2003 Mouse Stomodeum/Oral ectoderm
ETS1 ETS1 Majerus 1992 Human T-cell
STAT3 STAT3 Narimatsu 2001 Mouse T-cell
CREB CREB1 Walker 1995 Rat Testicular/Sertoli
GATA3 GATA3 Zhou 2003 Human Th1/Th2
TTF1 TITF1 Oguchi 1998 Human Thyroid
FRA1 FOSL1 Casalino 2003 Rat Thyroid
CEBPD CEBPD Yamada 1999 Mouse  
CEBPD CEBPD Tanabe 2000 Rat  
GATA1 GATA1 Orkin 1995    
cREL REL Hannink 1990 Chicken  
GATA1 GATA1 Tsai 1991    
HES7 HES7 Bessho 2001 Mouse  

Mammalian Autoregulation References
Angel, P., Hattori, K., Smeal, T., and Karin, M. (1988). The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1. Cell 55, 875-885.

Aota, S., Nakajima, N., Sakamoto, R., Watanabe, S., Ibaraki, N., and Okazaki, K. (2003). Pax6 autoregulation mediated by direct interaction of Pax6 protein with the head surface ectoderm-specific enhancer of the mouse Pax6 gene. Dev Biol 257, 1-13.

Beland, M., Pilon, N., Houle, M., Oh, K., Sylvestre, J. R., Prinos, P., and Lohnes, D. (2004). Cdx1 autoregulation is governed by a novel Cdx1-LEF1 transcription complex. Mol Cell Biol 24, 5028-5038.

Benoit, V., Hellin, A. C., Huygen, S., Gielen, J., Bours, V., and Merville, M. P. (2000). Additive effect between NF-kappaB subunits and p53 protein for transcriptional activation of human p53 promoter. Oncogene 19, 4787-4794.


Berger, I., and Shaul, Y. (1994). The human junD gene is positively and selectively autoregulated. DNA Cell Biol 13, 249-255.

Berger, I., and Shaul, Y. (1998). c-Fos antagonizes the junD gene positive autoregulatory loop; a novel c-Fos role in promoter switching. Gene 211, 375-382.

Briancon, N., Bailly, A., Clotman, F., Jacquemin, P., Lemaigre, F. P., and Weiss, M. C. (2004). Expression of the alpha7 isoform of hepatocyte nuclear factor (HNF) 4 is activated by HNF6/OC-2 and HNF1 and repressed by HNF4alpha1 in the liver. J Biol Chem 279, 33398-33408.

Casalino, L., De Cesare, D., and Verde, P. (2003). Accumulation of Fra-1 in ras-transformed cells depends on both transcriptional autoregulation and MEK-dependent posttranslational stabilization. Mol Cell Biol 23, 4401-4415.

Castles, C. G., Oesterreich, S., Hansen, R., and Fuqua, S. A. (1997). Auto-regulation of the estrogen receptor promoter. J Steroid Biochem Mol Biol 62, 155-163.

Catena, R., Tiveron, C., Ronchi, A., Porta, S., Ferri, A., Tatangelo, L., Cavallaro, M., Favaro, R., Ottolenghi, S., Reinbold, R., et al. (2004). Conserved POU binding DNA sites in the Sox2 upstream enhancer regulate gene expression in embryonic and neural stem cells. J Biol Chem 279, 41846-41857.

Chen, R. P., Ingraham, H. A., Treacy, M. N., Albert, V. R., Wilson, L., and Rosenfeld, M. G. (1990). Autoregulation of pit-1 gene expression mediated by two cis-active promoter elements. Nature 346, 583-586.

Christy, R. J., Kaestner, K. H., Geiman, D. E., and Lane, M. D. (1991). CCAAT/enhancer binding protein gene promoter: binding of nuclear factors during differentiation of 3T3-L1 preadipocytes. Proc Natl Acad Sci U S A 88, 2593-2597.

Cogswell, P. C., Scheinman, R. I., and Baldwin, A. S., Jr. (1993). Promoter of the human NF-kappa B p50/p105 gene. Regulation by NF-kappa B subunits and by c-REL. J Immunol 150, 2794-2804.

Cripps, R. M., Lovato, T. L., and Olson, E. N. (2004). Positive autoregulation of the Myocyte enhancer factor-2 myogenic control gene during somatic muscle development in Drosophila. Dev Biol 267, 536-547.

Danilov, V., Blum, M., Schweickert, A., Campione, M., and Steinbeisser, H. (1998). Negative autoregulation of the organizer-specific homeobox gene goosecoid. J Biol Chem 273, 627-635.

Deffie, A., Wu, H., Reinke, V., and Lozano, G. (1993). The tumor suppressor p53 regulates its own transcription. Mol Cell Biol 13, 3415-3423.

Doan, L. L., Porter, S. D., Duan, Z., Flubacher, M. M., Montoya, D., Tsichlis, P. N., Horwitz, M., Gilks, C. B., and Grimes, H. L. (2004). Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells. Nucleic Acids Res 32, 2508-2519.

Facchini, L. M., Chen, S., Marhin, W. W., Lear, J. N., and Penn, L. Z. (1997). The Myc negative autoregulation mechanism requires Myc-Max association and involves the c-myc P2 minimal promoter. Mol Cell Biol 17, 100-114.

Fitch, M. J., Donato, J. J., and Tye, B. K. (2003). Mcm7, a subunit of the presumptive MCM helicase, modulates its own expression in conjunction with Mcm1. J Biol Chem 278, 25408-25416.

Foka, P., Kousteni, S., and Ramji, D. P. (2001). Molecular characterization of the Xenopus CCAAT-enhancer binding protein beta gene promoter. Biochem Biophys Res Commun 285, 430-436.

Goodyer, C. G., Tremblay, J. J., Paradis, F. W., Marcil, A., Lanctot, C., Gauthier, Y., and Drouin, J. (2003). Pitx1 in vivo promoter activity and mechanisms of positive autoregulation. Neuroendocrinology 78, 129-137.

Grad, J. M., Dai, J. L., Wu, S., and Burnstein, K. L. (1999). Multiple androgen response elements and a Myc consensus site in the androgen receptor (AR) coding region are involved in androgen-mediated up-regulation of AR messenger RNA. Mol Endocrinol 13, 1896-1911.

Grass, J. A., Boyer, M. E., Pal, S., Wu, J., Weiss, M. J., and Bresnick, E. H. (2003). GATA-1-dependent transcriptional repression of GATA-2 via disruption of positive autoregulation and domain-wide chromatin remodeling. Proc Natl Acad Sci U S A 100, 8811-8816.

Hamel, P. A., Gill, R. M., Phillips, R. A., and Gallie, B. L. (1992). Transcriptional repression of the E2-containing promoters EIIaE, c-myc, and RB1 by the product of the RB1 gene. Mol Cell Biol 12, 3431-3438.

Hannink, M., and Temin, H. M. (1990). Structure and autoregulation of the c-rel promoter. Oncogene 5, 1843-1850. Hatzis, P., and Talianidis, I. (2001). Regulatory mechanisms controlling human hepatocyte nuclear factor 4alpha gene expression. Mol Cell Biol 21, 7320-7330.

Henningfeld, K. A., Friedle, H., Rastegar, S., and Knochel, W. (2002). Autoregulation of Xvent-2B; direct interaction and functional cooperation of Xvent-2 and Smad1. J Biol Chem 277, 2097-2103.

Hirata, H., Yoshiura, S., Ohtsuka, T., Bessho, Y., Harada, T., Yoshikawa, K., and Kageyama, R. (2002). Oscillatory expression of the bHLH factor Hes1 regulated by a negative feedback loop. Science 298, 840-843.

Hudson, J. M., Frade, R., and Bar-Eli, M. (1995). Wild-type p53 regulates its own transcription in a cell-type specific manner. DNA Cell Biol 14, 759-766.

Ingraham, H. A., Chen, R. P., Mangalam, H. J., Elsholtz, H. P., Flynn, S. E., Lin, C. R., Simmons, D. M., Swanson, L., and Rosenfeld, M. G. (1988). A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype. Cell 55, 519-529.

Jeong, J. H., Orvis, J., Kim, J. W., McMurtrey, C. P., Renne, R., and Dittmer, D. P. (2004). Regulation and autoregulation of the promoter for the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus. J Biol Chem 279, 16822-16831.

Jorcyk, C. L., Watson, D. K., Mavrothalassitis, G. J., and Papas, T. S. (1991). The human ETS1 gene: genomic structure, promoter characterization and alternative splicing. Oncogene 6, 523-532.

Kitaura, H., Galli, I., Taira, T., Iguchi-Ariga, S. M., and Ariga, H. (1991). Activation of c-myc promoter by c-myc protein in serum starved cells. FEBS Lett 290, 147-152.

Konig, H., Ponta, H., Rahmsdorf, U., Buscher, M., Schonthal, A., Rahmsdorf, H. J., and Herrlich, P. (1989). Autoregulation of fos: the dyad symmetry element as the major target of repression. Embo J 8, 2559-2566.

Kume, K., Zylka, M. J., Sriram, S., Shearman, L. P., Weaver, D. R., Jin, X., Maywood, E. S., Hastings, M. H., and Reppert, S. M. (1999). mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell 98, 193-205.

Laffitte, B. A., Joseph, S. B., Walczak, R., Pei, L., Wilpitz, D. C., Collins, J. L., and Tontonoz, P. (2001). Autoregulation of the human liver X receptor alpha promoter. Mol Cell Biol 21, 7558-7568.

Legraverend, C., Antonson, P., Flodby, P., and Xanthopoulos, K. G. (1993). High level activity of the mouse CCAAT/enhancer binding protein (C/EBP alpha) gene promoter involves autoregulation and several ubiquitous transcription factors. Nucleic Acids Res 21, 1735-1742.

Li, Y., Bolten, C., Bhat, B. G., Woodring-Dietz, J., Li, S., Prayaga, S. K., Xia, C., and Lala, D. S. (2002). Induction of human liver X receptor alpha gene expression via an autoregulatory loop mechanism. Mol Endocrinol 16, 506-514.

Lombardi, L., Ciana, P., Cappellini, C., Trecca, D., Guerrini, L., Migliazza, A., Maiolo, A. T., and Neri, A. (1995). Structural and functional characterization of the promoter regions of the NFKB2 gene. Nucleic Acids Res 23, 2328-2336.

Mahatan, C. S., Kaestner, K. H., Geiman, D. E., and Yang, V. W. (1999). Characterization of the structure and regulation of the murine gene encoding gut-enriched Kruppel-like factor (Kruppel-like factor 4). Nucleic Acids Res 27, 4562-4569.

Majerus, M. A., Bibollet-Ruche, F., Telliez, J. B., Wasylyk, B., and Bailleul, B. (1992). Serum, AP-1 and Ets-1 stimulate the human ets-1 promoter. Nucleic Acids Res 20, 2699-2703.

Martinotti, S., Richman, A., and Hayday, A. (1988). Disruption of the putative c-myc auto-regulation mechanism in a human B cell line. Curr Top Microbiol Immunol 141, 264-268.

Mechta, F. a. Y., M. (1994). In The Fos and Jun Families of Transcription Factors, P. E. a. H. Angel, P.A., ed. (Boca Raton, CRC Press), pp. 115.

Meyer, T. E., Waeber, G., Lin, J., Beckmann, W., and Habener, J. F. (1993). The promoter of the gene encoding 3',5'-cyclic adenosine monophosphate (cAMP) response element binding protein contains cAMP response elements: evidence for positive autoregulation of gene transcription. Endocrinology 132, 770-780.

Molina, C. A., Foulkes, N. S., Lalli, E., and Sassone-Corsi, P. (1993). Inducibility and negative autoregulation of CREM: an alternative promoter directs the expression of ICER, an early response repressor. Cell 75, 875-886.

Muralidharan, V., Sweet, T., Nadraga, Y., Amini, S., and Khalili, K. (2001). Regulation of Puralpha gene transcription: evidence for autoregulation of Puralpha promoter. J Cell Physiol 186, 406-413.

Narimatsu, M., Maeda, H., Itoh, S., Atsumi, T., Ohtani, T., Nishida, K., Itoh, M., Kamimura, D., Park, S. J., Mizuno, K., et al. (2001). Tissue-specific autoregulation of the stat3 gene and its role in interleukin-6-induced survival signals in T cells. Mol Cell Biol 21, 6615-6625.

Neuman, E., Flemington, E. K., Sellers, W. R., and Kaelin, W. G., Jr. (1994). Transcription of the E2F-1 gene is rendered cell cycle dependent by E2F DNA-binding sites within its promoter. Mol Cell Biol 14, 6607-6615.

Nicolaides, N. C., Gualdi, R., Casadevall, C., Manzella, L., and Calabretta, B. (1991). Positive autoregulation of c-myb expression via Myb binding sites in the 5' flanking region of the human c-myb gene. Mol Cell Biol 11, 6166-6176.

Niehof, M., Kubicka, S., Zender, L., Manns, M. P., and Trautwein, C. (2001). Autoregulation enables different pathways to control CCAAT/enhancer binding protein beta (C/EBP beta) transcription. J Mol Biol 309, 855-868.

Nishikawa, K., Kobayashi, M., Masumi, A., Lyons, S. E., Weinstein, B. M., Liu, P. P., and Yamamoto, M. (2003). Self-association of Gata1 enhances transcriptional activity in vivo in zebra fish embryos. Mol Cell Biol 23, 8295-8305.

Oberkofler, H., Schraml, E., Krempler, F., and Patsch, W. (2003). Potentiation of liver X receptor transcriptional activity by peroxisome-proliferator-activated receptor gamma co-activator 1 alpha. Biochem J 371, 89-96.

Oguchi, H., and Kimura, S. (1998). Multiple transcripts encoded by the thyroid-specific enhancer-binding protein (T/EBP)/thyroid-specific transcription factor-1 (TTF-1) gene: evidence of autoregulation. Endocrinology 139, 1999-2006.

Ohtani-Fujita, N., Fujita, T., Takahashi, R., Robbins, P. D., Dryja, T. P., and Sakai, T. (1994). A silencer element in the retinoblastoma tumor-suppressor gene. Oncogene 9, 1703-1711.

Oka, T., Komuro, I., Shiojima, I., Hiroi, Y., Mizuno, T., Aikawa, R., Akazawa, H., Yamazaki, T., and Yazaki, Y. (1997). Autoregulation of human cardiac homeobox gene CSX1: mediation by the enhancer element in the first intron. Heart Vessels Suppl 12, 10-14.

Oka, T., Rairkar, A., and Chen, J. H. (1991). Structural and functional analysis of the regulatory sequences of the ets-1 gene. Oncogene 6, 2077-2083.

Okumura-Nakanishi, S., Saito, M., Niwa, H., and Ishikawa, F. (2005). Oct-3/4 and Sox2 regulate Oct-3/4 gene in embryonic stem cells. J Biol Chem 280, 5307-5317.

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Sassone-Corsi, P., Sisson, J. C., and Verma, I. M. (1988). Transcriptional autoregulation of the proto-oncogene fos. Nature 334, 314-319.

Schuettengruber, B., Simboeck, E., Khier, H., and Seiser, C. (2003). Autoregulation of mouse histone deacetylase 1 expression. Mol Cell Biol 23, 6993-7004.

Sears, R., Ohtani, K., and Nevins, J. R. (1997). Identification of positively and negatively acting elements regulating expression of the E2F2 gene in response to cell growth signals. Mol Cell Biol 17, 5227-5235.

Shan, B., Chang, C. Y., Jones, D., and Lee, W. H. (1994). The transcription factor E2F-1 mediates the autoregulation of RB gene expression. Mol Cell Biol 14, 299-309.

Sivak, L. E., Tai, K. F., Smith, R. S., Dillon, P. A., Brodeur, G. M., and Carroll, W. L. (1997). Autoregulation of the human N-myc oncogene is disrupted in amplified but not single-copy neuroblastoma cell lines. Oncogene 15, 1937-1946.

Smith, J. E., 3rd, and Cronmiller, C. (2001). The Drosophila daughterless gene autoregulates and is controlled by both positive and negative cis regulation. Development 128, 4705-4714.

Spencer, J. A., and Misra, R. P. (1996). Expression of the serum response factor gene is regulated by serum response factor binding sites. J Biol Chem 271, 16535-16543.

Tanabe, A., Kumahara, C., Osada, S., Nishihara, T., and Imagawa, M. (2000). Gene expression of CCAAT/enhancer-binding protein delta mediated by autoregulation is repressed by related gene family proteins. Biol Pharm Bull 23, 1424-1429.

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Thayer, M. J., Tapscott, S. J., Davis, R. L., Wright, W. E., Lassar, A. B., and Weintraub, H. (1989). Positive autoregulation of the myogenic determination gene MyoD1. Cell 58, 241-248.

Theill, L. E., and Karin, M. (1993). Transcriptional control of GH expression and anterior pituitary development. Endocr Rev 14, 670-689.

Timchenko, N., Wilson, D. R., Taylor, L. R., Abdelsayed, S., Wilde, M., Sawadogo, M., and Darlington, G. J. (1995). Autoregulation of the human C/EBP alpha gene by stimulation of upstream stimulatory factor binding. Mol Cell Biol 15, 1192-1202.

Trieu, M., Ma, A., Eng, S. R., Fedtsova, N., and Turner, E. E. (2003). Direct autoregulation and gene dosage compensation by POU-domain transcription factor Brn3a. Development 130, 111-121.

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Walker, W. H., Fucci, L., and Habener, J. F. (1995). Expression of the gene encoding transcription factor cyclic adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB): regulation by follicle-stimulating hormone-induced cAMP signaling in primary rat Sertoli cells. Endocrinology 136, 3534-3545.

Wang, X., Li, Z., Naganuma, A., and Ye, B. H. (2002). Negative autoregulation of BCL-6 is bypassed by genetic alterations in diffuse large B cell lymphomas. Proc Natl Acad Sci U S A 99, 15018-15023.

Xu, F., Li, H., and Jin, T. (1999). Cell type-specific autoregulation of the Caudal-related homeobox gene Cdx-2/3. J Biol Chem 274, 34310-34316.

Yamaguchi, Y., Sawada, J., Yamada, M., Handa, H., and Azuma, N. (1997). Autoregulation of Pax6 transcriptional activation by two distinct DNA-binding subdomains of the paired domain. Genes Cells 2, 255-261.

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