The N Termini of Friend of GATA (FOG) Proteins Define a Novel Transcriptional Repression Motif and a Superfamily of Transcriptional Repressors

Abstract

Members of the Friend of GATA (FOG) family of transcriptional co-factors are required for the development of both the cardiovascular and hematopoietic systems. FOG proteins physically interact with members of the GATA family of transcriptional activators and modulate their activity. We have previously shown that FOG-2 can bind to the N-terminal zinc finger of GATA4 and, via this interaction, repress GATA4-mediated transcriptional activation of various cardiac promoters. In this report we further characterize the domain of FOG-2 necessary for repression of GATA4 transcriptional activity. We show that FOG-2-mediated repression is not blocked by the histone deacetylase inhibitor tricostatin A, suggesting that FOG-2 repression of GATA4 occurs via a histone deacetylase independent mechanism. N-terminal deletion mutants of FOG-2 revealed that the first 12 amino acids of FOG-2 are necessary for FOG-2-mediated repression. Fusion of these 12 amino acids to the DNA binding domain of GAL4 demonstrated that this region is sufficient to mediate transcriptional repression even when recruited to a heterologous promoter. Single amino acid substitutions within this N-terminal domain of FOG-2 defined the critical amino acid sequence as RRKQxxPxxI. Interestingly, a search of the NCBI protein data base identified several other partially characterized zinc finger transcriptional repressors from various vertebrate species that contained this motif at their N terminus. Taken together, these observations define a novel transcriptional repression motif and a superfamily of zinc finger transcriptional repressors. Members of the Friend of GATA (FOG) family of transcriptional co-factors are required for the development of both the cardiovascular and hematopoietic systems. FOG proteins physically interact with members of the GATA family of transcriptional activators and modulate their activity. We have previously shown that FOG-2 can bind to the N-terminal zinc finger of GATA4 and, via this interaction, repress GATA4-mediated transcriptional activation of various cardiac promoters. In this report we further characterize the domain of FOG-2 necessary for repression of GATA4 transcriptional activity. We show that FOG-2-mediated repression is not blocked by the histone deacetylase inhibitor tricostatin A, suggesting that FOG-2 repression of GATA4 occurs via a histone deacetylase independent mechanism. N-terminal deletion mutants of FOG-2 revealed that the first 12 amino acids of FOG-2 are necessary for FOG-2-mediated repression. Fusion of these 12 amino acids to the DNA binding domain of GAL4 demonstrated that this region is sufficient to mediate transcriptional repression even when recruited to a heterologous promoter. Single amino acid substitutions within this N-terminal domain of FOG-2 defined the critical amino acid sequence as RRKQxxPxxI. Interestingly, a search of the NCBI protein data base identified several other partially characterized zinc finger transcriptional repressors from various vertebrate species that contained this motif at their N terminus. Taken together, these observations define a novel transcriptional repression motif and a superfamily of zinc finger transcriptional repressors. It is becoming apparent that transcriptional repression plays an important role in the development of organ systems in many different model organisms. In Drosophila, the repressors knirps and even-skipped have been shown to be critical for the initial formation of body segments within the developing embryo (1Clyde D.E. Corado M.S. Wu X. Pare A. Papatsenko D. Small S. Nature. 2003; 426: 849-853Crossref PubMed Scopus (159) Google Scholar, 2Frasch M. Warrior R. Tugwood J. Levine M. Genes Dev. 1988; 2: 1824-1838Crossref PubMed Scopus (78) Google Scholar). In mammals, the transcriptional repressor N-CoR is critical for normal thymocyte, erythrocyte, and central nervous system development (3Jepsen K. Hermanson O. Onami T.M. Gleiberman A.S. Lunyak V. McEvilly R.J. Kurokawa R. Kumar V. Liu F. Seto E. Hedrick S.M. Mandel G. Glass C.K. Rose D.W. Rosenfeld M.G. Cell. 2000; 102: 753-763Abstract Full Text Full Text PDF PubMed Scopus (429) Google Scholar), whereas chicken ovalbumin upstream promoter transcription factor II (coup-TFII) is required for the development of the heart and vascular system (4Pereira F.A. Qiu Y. Zhou G. Tsai M.J. Tsai S.Y. Genes Dev. 1999; 13: 1037-1049Crossref PubMed Scopus (415) Google Scholar). Transcriptional repressors can be broadly categorized into three classes; those that inhibit the basal transcriptional machinery, those that block the function of activators, and those that modulate chromatin structure (5Gaston K. Jayaraman P.S. Cell. Mol. Life Sci. 2003; 60: 721-741Crossref PubMed Scopus (101) Google Scholar). Inhibitors of the basal transcriptional machinery include even-skipped, which is thought to block transcription by binding directly to TATA-binding protein (TBP) 1The abbreviations used are: TBP, TATA-binding protein; HDAC, histone deacetylase; CtBP, C-terminal-binding protein; FOG, Friend of GATA; ANF, atrial naturetic factor; hGH, human growth hormone; TSA, tricostatin A. and preventing TBP interaction with the TATA box (6Li C. Manley J.L. Mol. Cell. Biol. 1998; 18: 3771-3781Crossref PubMed Scopus (52) Google Scholar). An example of a repressor that functions through blocking a transcriptional activator is the repressor Id, which inhibits transcription by binding to other basic helix-loop-helix-containing transcriptional activators and blocking their ability to bind DNA (7Benezra R. Davis R.L. Lockshon D. Turner D.L. Weintraub H. Cell. 1990; 61: 49-59Abstract Full Text PDF PubMed Scopus (1804) Google Scholar). Inhibitors of activator activity may also function by increasing activator degradation or altering the subcellular localization of the activator (5Gaston K. Jayaraman P.S. Cell. Mol. Life Sci. 2003; 60: 721-741Crossref PubMed Scopus (101) Google Scholar). Finally, repressors that alter chromatin structure are often dependent on histone deacetylases (HDACs) and include repressors such as retinoblastoma tumor suppressor protein (Rb) and C-terminal-binding protein (CtBP) (8Brehm A. Miska E.A. McCance D.J. Reid J.L. Bannister A.J. Kouzarides T. Nature. 1998; 391: 597-601Crossref PubMed Scopus (1080) Google Scholar, 9Luo R.X. Postigo A.A. Dean D.C. Cell. 1998; 92: 463-473Abstract Full Text Full Text PDF PubMed Scopus (839) Google Scholar, 10Shi Y. Sawada J. Sui G. Affar el B. Whetstine J.R. Lan F. Ogawa H. Luke M.P. Nakatani Y. Nature. 2003; 422: 735-738Crossref PubMed Scopus (644) Google Scholar). Repressors such as these are thought to function by recruiting various HDACs to the local chromatin, resulting in the deacetylation of the N-terminal tail of the histones within that chromatin region, leading to a more condensed chromatin structure and inhibiting access of other transcriptional activators to the target gene. Other mechanisms of chromatin remodeling include the inhibition of histone acetyltransferases or the recruitment and activation of histone methyltransferases (5Gaston K. Jayaraman P.S. Cell. Mol. Life Sci. 2003; 60: 721-741Crossref PubMed Scopus (101) Google Scholar). It is likely that we are just beginning to realize the complexity of repressive mechanisms involved in the regulation of development. The FOG family of proteins are transcriptional co-factors that have been shown to be critical for development of the hematopoietic as well as cardiovascular system in flies, frogs, and mice (11Tevosian S.G. Deconinck A.E. Tanaka M. Schinke M. Litovsky S.H. Izumo S. Fujiwara Y. Orkin S.H. Cell. 2000; 101: 729-739Abstract Full Text Full Text PDF PubMed Scopus (350) Google Scholar, 12Svensson E.C. Huggins G.S. Lin H. Clendenin C. Jiang F. Tufts R. Dardik F.B. Leiden J.M. Nat. Genet. 2000; 25: 353-356Crossref PubMed Scopus (153) Google Scholar, 13Tsang A.P. Fujiwara Y. Hom D.B. Orkin S.H. Genes Dev. 1998; 12: 1176-1188Crossref PubMed Scopus (299) Google Scholar, 14Fossett N. Tevosian S.G. Gajewski K. Zhang Q. Orkin S.H. Schulz R.A. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 7342-7347Crossref PubMed Scopus (132) Google Scholar, 15Deconinck A.E. Mead P.E. Tevosian S.G. Crispino J.D. Katz S.G. Zon L.I. Orkin S.H. Development. 2000; 127: 2031-2040PubMed Google Scholar). Indeed, mice deficient in FOG-1 fail to form mature erythrocytes or megakaryocytes and die at embryonic day (E) 11.5 due to severe anemia (13Tsang A.P. Fujiwara Y. Hom D.B. Orkin S.H. Genes Dev. 1998; 12: 1176-1188Crossref PubMed Scopus (299) Google Scholar). FOG-1 also plays a role in heart development as mice with a FOG-1 gene disruption in the developing cardiac and vascular endothelium die at E14.5 secondary to a double outlet right ventricle and a common atrioventricular valve (16Katz S.G. Williams A. Yang J. Fujiwara Y. Tsang A.P. Epstein J.A. Orkin S.H. Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 14030-14035Crossref PubMed Scopus (34) Google Scholar). Mice deficient in FOG-2 die in utero at E13.5 of cardiac malformations that include a double outlet right ventricle, pulmonic stenosis, a common atrioventricular valve, ventricular wall hypoplasia, and lack of coronary arteries (11Tevosian S.G. Deconinck A.E. Tanaka M. Schinke M. Litovsky S.H. Izumo S. Fujiwara Y. Orkin S.H. Cell. 2000; 101: 729-739Abstract Full Text Full Text PDF PubMed Scopus (350) Google Scholar, 12Svensson E.C. Huggins G.S. Lin H. Clendenin C. Jiang F. Tufts R. Dardik F.B. Leiden J.M. Nat. Genet. 2000; 25: 353-356Crossref PubMed Scopus (153) Google Scholar). Taken together, these results demonstrate the importance of FOG proteins for the development of the hematopoietic and cardiovascular system. All FOG proteins contain multiple zinc finger domains and physically interact with members of the GATA family of transcriptional activators (17Tevosian S.G. Deconinck A.E. Cantor A.B. Rieff H.I. Fujiwara Y. Corfas G. Orkin S.H. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 950-955Crossref PubMed Scopus (179) Google Scholar, 18Svensson E.C. Tufts R.L. Polk C.E. Leiden J.M. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 956-961Crossref PubMed Scopus (241) Google Scholar, 19Lu J.R. McKinsey T.A. Xu H. Wang D.Z. Richardson J.A. Olson E.N. Mol. Cell. Biol. 1999; 19: 4495-4502Crossref PubMed Scopus (181) Google Scholar, 20Fox A.H. Liew C. Holmes M. Kowalski K. Mackay J. Crossley M. EMBO J. 1999; 18: 2812-2822Crossref PubMed Scopus (225) Google Scholar, 21Fossett N. Schulz R.A. Trends Cardiovasc. Med. 2001; 11: 185-190Crossref PubMed Scopus (36) Google Scholar). FOG proteins specifically bind to the N-terminal zinc finger of GATA factors, and this interaction can be disrupted by point mutations within this zinc finger (18Svensson E.C. Tufts R.L. Polk C.E. Leiden J.M. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 956-961Crossref PubMed Scopus (241) Google Scholar, 22Crispino J.D. Lodish M.B. MacKay J.P. Orkin S.H. Mol. Cell. 1999; 3: 219-228Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar). Mice homozygous for such mutations in GATA4 die in utero of congenital heart defects that are similar to those seen in FOG-2-deficient mice (23Crispino J.D. Lodish M.B. Thurberg B.L. Litovsky S.H. Collins T. Molkentin J.D. Orkin S.H. Genes Dev. 2001; 15: 839-844Crossref PubMed Scopus (258) Google Scholar). Furthermore, mice with mutations in the N-terminal zinc fingers of GATA1 and GATA2 recapitulate the phenotype seen in FOG-1-deficient mice (24Chang A.N. Cantor A.B. Fujiwara Y. Lodish M.B. Droho S. Crispino J.D. Orkin S.H. Proc. Natl. Acad. Sci. U. S. A. 2002; 99: 9237-9242Crossref PubMed Scopus (151) Google Scholar). These results support the notion that interaction with GATA factors is required for function of FOG proteins in development. The FOG-GATA interaction can result in either repression or synergistic activation of target promoters (18Svensson E.C. Tufts R.L. Polk C.E. Leiden J.M. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 956-961Crossref PubMed Scopus (241) Google Scholar, 19Lu J.R. McKinsey T.A. Xu H. Wang D.Z. Richardson J.A. Olson E.N. Mol. Cell. Biol. 1999; 19: 4495-4502Crossref PubMed Scopus (181) Google Scholar, 25Tsang A.P. Visvader J.E. Turner C.A. Fujiwara Y. Yu C. Weiss M.J. Crossley M. Orkin S.H. Cell. 1997; 90: 109-119Abstract Full Text Full Text PDF PubMed Scopus (626) Google Scholar, 26Wang X. Crispino J.D. Letting D.L. Nakazawa M. Poncz M. Blobel G.A. EMBO J. 2002; 21: 5225-5234Crossref PubMed Scopus (142) Google Scholar, 27Zhou M. Ouyang W. Gong Q. Katz S.G. White J.M. Orkin S.H. Murphy K.M. J. Exp. Med. 2001; 194: 1461-1471Crossref PubMed Scopus (80) Google Scholar, 28Svensson E.C. Huggins G.S. Dardik F.B. Polk C.E. Leiden J.M. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, 2002; PubMed Scopus Google Scholar, Y. K. Cardiovasc. 2003; 60: PubMed Scopus Google Scholar, M. H. M. Biol. 2003; PubMed Scopus Google Scholar). that the of a binding for the transcription factor in to a GATA can FOG-1 from a to a X. Crispino J.D. Letting D.L. Nakazawa M. Poncz M. Blobel G.A. EMBO J. 2002; 21: 5225-5234Crossref PubMed Scopus (142) Google Scholar). in and promoter to FOG proteins as transcriptional the ability of GATA factors to for this repression be the recruitment of other transcriptional repressors to the promoter such repressor is the chicken ovalbumin upstream promoter transcription factor which been shown to interact with a domain of FOG-2 that zinc fingers and G.S. J. R. Leiden J.M. J. Biol. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). a form of FOG-2 this domain is to mediate repression in E.C. Huggins G.S. Dardik F.B. Polk C.E. Leiden J.M. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). FOG proteins have also been shown to interact with the FOG-1 and FOG-2 have binding for proteins and have been shown to interact with in A.E. Mead P.E. Tevosian S.G. Crispino J.D. Katz S.G. Zon L.I. Orkin S.H. Development. 2000; 127: 2031-2040PubMed Google Scholar, 20Fox A.H. Liew C. Holmes M. Kowalski K. Mackay J. Crossley M. EMBO J. 1999; 18: 2812-2822Crossref PubMed Scopus (225) Google Scholar, 28Svensson E.C. Huggins G.S. Dardik F.B. Polk C.E. Leiden J.M. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, S.G. Cantor A.B. Orkin S.H. Mol. Cell. Biol. 2002; PubMed Scopus Google Scholar). disruption of this interaction by not the ability of FOG-2 to repress transcription in A.H. Liew C. Holmes M. Kowalski K. Mackay J. Crossley M. EMBO J. 1999; 18: 2812-2822Crossref PubMed Scopus (225) Google Scholar, 28Svensson E.C. Huggins G.S. Dardik F.B. Polk C.E. Leiden J.M. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). In disruption of the domain of FOG-1 in mice results in hematopoietic suggesting that the interaction is not required for or development S.G. Cantor A.B. Orkin S.H. Mol. Cell. Biol. 2002; PubMed Scopus Google Scholar). the by which FOG proteins mediate transcriptional repression is and In we demonstrated that a transcriptional repression domain also in the N of FOG-1 and FOG-2 E.C. Huggins G.S. Dardik F.B. Polk C.E. Leiden J.M. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). In this report we further characterize this repression domain and to the first 12 amino acids within FOG We show this domain to be both necessary and sufficient to mediate transcriptional repression when to a heterologous DNA binding We demonstrate that this repression is in an and define the critical amino acid within this domain that are required for repression. Furthermore, we demonstrate that these amino acids are vertebrate species in the FOG proteins and have identified this repression motif in other partially characterized zinc finger transcriptional repressors. Taken together, these observations define a novel transcriptional repression family and a repression motif that may be critical in a of and FOG-2 have been previously E.C. Huggins G.S. Dardik F.B. Polk C.E. Leiden J.M. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). for FOG-2 proteins and the with or The resulting with and and into a the of the region of FOG-2 from FOG-2 into the to the for the as the N-terminal amino acids of FOG-2 the and FOG-2 as with the and into the of the and the into the of the and and used to a of the GAL4 DNA binding domain from M. PubMed Scopus Google Scholar). into the of of the to for All by DNA and at in and a and the day of of of of of FOG-2 or FOG-2 mutants and to a of of DNA with of and of and to with of growth the of of of and of the of the with and of growth tricostatin in the with and growth with an of tricostatin or with and of to the a at from the and of this used in a protein to protein activity in by of with and of and and at in a with at activity as the in and to the protein in the activity of and of and in a growth of and a promoter activity as the by the activity. FOG-2-mediated of GATA4 a first in the of the repression domain of we used the tricostatin to the of FOG-2 on activity. been previously shown to inhibit both and II HDACs and transcriptional repression through M. A. Y. N. Med. 2003; PubMed Scopus (132) Google Scholar, M. S. T. PubMed Scopus Google Scholar). we have shown FOG-2 is an repressor of GATA4-mediated of the promoter in first and The of from to on the ability of FOG-2 to repress GATA4 of the promoter through These results support the notion that FOG-2 transcription an in of the N-terminal of FOG demonstrated that both FOG-1 and FOG-2 of GATA4 of the promoter and that this repression required the N of protein E.C. Huggins G.S. Dardik F.B. Polk C.E. Leiden J.M. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). Furthermore, protein the DNA binding domain of GAL4 and the N of FOG-2 demonstrated that the N-terminal amino acids sufficient to mediate transcriptional repression in a heterologous system E.C. Huggins G.S. Dardik F.B. Polk C.E. Leiden J.M. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). further the repression domain within the first amino acids of FOG we that the amino acids within this domain critical for repression be in sequence such we first the NCBI and data base for the of FOG proteins from other We identified or sequence the N-terminal amino acids of FOG-2 from both human and we identified from and the of amino acid from of these and can be of the first are in of these suggesting that the amino acids critical for repression in the first amino acids of the FOG of the in the N of the importance of the region of the N of FOG-2 for transcriptional we a a FOG-2 protein that amino acids and the ability of this protein to repress in a as previously (18Svensson E.C. Tufts R.L. Polk C.E. Leiden J.M. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 956-961Crossref PubMed Scopus (241) Google Scholar, 28Svensson E.C. Huggins G.S. Dardik F.B. Polk C.E. Leiden J.M. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). can be seen in the of amino acids the ability of FOG-2 to repress transcription the and result that the first amino acids are required for FOG-2 repression. further characterize the N-terminal repression we substitutions in amino acids or of These proteins also for their ability to repress GATA4 as shown in of amino acids or in of repression by FOG-2 and whereas of amino acids in FOG-2 repression and These results further the critical region to the first 12 amino we substitutions in of amino acid or in a of repression by whereas of amino acids or on repressive activity of amino acids and 12 in a of repression that and the of FOG-2 as a transcriptional FOG-2 necessary to repression. a of these not be by of shown to of FOG-2 in when at not These results that amino acids and 12 are required for FOG-2 repression. these amino acids are in FOG proteins species as shown in The N-terminal 12 to Transcriptional the critical repression motif of FOG proteins identified is sufficient to mediate transcriptional we the first or 12 amino acids of FOG-2 to the DNA binding domain of the transcription factor GAL4 These into with a the gene the of a promoter with of the GAL4 DNA binding with when the first amino acids of FOG-2 to the resulting protein an transcriptional inhibiting promoter activity by first and results just the first amino acids of FOG-2 first 12 amino acids Furthermore, a protein the first 12 amino acids of FOG-2 with an at is to repress the promoter similar of protein to the not Taken together, these results define the critical repression motif in the N of FOG proteins as RRKQxxPxxI. of the FOG in Other Transcriptional the critical of the FOG repression motif we the NCBI data base for other proteins that contain this The results are shown in We identified proteins from multiple vertebrate species that contain this this motif not in proteins from the or Interestingly, of the proteins identified in this search contain zinc finger and many have been previously characterized as transcriptional repressors D. A. K. D.J. J.E. M. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, S.M. Yang J. M. J. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, J. 1997; PubMed Google Scholar). In the FOG repression motif in of these proteins is at the N of Finally, of the critical identified in with the of the at 12 in the several of the identified proteins a of for or other amino acids such as or Taken together, these results demonstrate that the FOG repression motif is in other zinc transcriptional repressors and, define a novel vertebrate superfamily of zinc finger transcriptional repressors that include members of both the FOG and In this we have further characterized the N-terminal repression domain of FOG-2 and have a novel repression motif in both FOG-1 and FOG-2 that is vertebrate In we have identified this motif in other transcriptional suggesting that this motif may be as a of transcriptional repression. to through an as tricostatin A, a to block repression by It is that the FOG repression motif may function in chromatin remodeling by the blocking of histone acetyltransferases or the activation of histone motif may also function either by directly with the basal transcriptional machinery or or recruiting a to the promoter are to this The N of FOG-1 been previously shown to be required for development A.B. Katz S.G. Orkin S.H. Mol. Cell. Biol. 2002; PubMed Scopus Google Scholar). an in hematopoietic with FOG-1-deficient embryonic Cantor A.B. Katz S.G. Orkin S.H. Mol. Cell. Biol. 2002; PubMed Scopus Google demonstrated that the N-terminal amino acids of FOG-1 is not required for of in the of is critical for from these result in with the in this report that the FOG repression motif may a role in the regulation of also that the FOG repression motif may not be in for which FOG proteins are In is FOG family N. Tevosian S.G. Gajewski K. Zhang Q. Orkin S.H. Schulz R.A. Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 7342-7347Crossref PubMed Scopus (132) Google Scholar, M. Y. F. Y. Genes Dev. 1997; 11: PubMed Scopus Google Scholar, N. Zhang Q. Gajewski K. Y. Schulz R.A. Proc. Natl. Acad. Sci. U. S. A. 2000; PubMed Scopus Google Scholar, N. K. Gajewski K. Orkin S.H. Schulz R.A. Proc. Natl. Acad. Sci. U. S. 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It been shown to contain repression of which is to the N-terminal amino The FOG repression motif is by the N-terminal 12 amino acids in this is that this motif is for the repression activity for this with observations with the repression by the N of is Finally, the transcriptional repressor is example of a zinc finger transcriptional repressor that the FOG repression is critical for the development of the and mutations in in R. Y. K. K. A. D.J. S. D.L. M. M. T. Development. 2001; PubMed Google Scholar, J. A. H. U. W. Nat. Genet. 1998; 18: PubMed Scopus Google Scholar, S.M. Yang J. J. M. Mol. Genet. 2003; 12: PubMed Scopus Google Scholar). on this protein demonstrated that the repression domain to the N-terminal amino acids S.M. Yang J. J. M. Mol. Genet. 2003; 12: PubMed Scopus Google Scholar). with the FOG repression motif of is to the N of the In to FOG-2 and the N-terminal amino acids of shown to interact with and the repression by this domain partially blocked by the inhibitor S.M. Yang J. M. J. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, S.M. Yang J. J. M. Mol. Genet. 2003; 12: PubMed Scopus Google Scholar). that this domain repress transcription by that is and the other by an mechanism. the of a FOG repression motif within this the likely functions through this the of other species are and is that other proteins the FOG repression motif be