Sumoylation of MITF and Its Related Family Members TFE3 and TFEB

MITF and its related family members TFE3 and TFEB heterodimerize with each other, recognize the same DNA sequences, and are subject to many of the same post-translational modifications. We show that lysine residues within conserved small ubiquitin-like modifier (SUMO) consensus sites in these family members are subject to SUMO modification. Mutation of these sites significantly affects the transcriptional activity of MITF but does not alter dimerization, DNA binding, stability, or nuclear localization. Mutagenesis reducing the number of MITF binding sites in the promoter of TRPM1 from three to one eliminated the difference in transcriptional activity between the MITF mutants. Among other MITF target gene promoter constructs, differences in transcriptional activity between wild type and non-sumoylatable MITF were only seen in promoters with multiple MITF binding sites. These data support a synergy control model in which the functional consequences of MITF sumoylation depend on promoter context. Sumoylation, thus, provides a possible mechanism for altering the effects of MITF by affecting the target genes that it activates. MITF and its related family members TFE3 and TFEB heterodimerize with each other, recognize the same DNA sequences, and are subject to many of the same post-translational modifications. We show that lysine residues within conserved small ubiquitin-like modifier (SUMO) consensus sites in these family members are subject to SUMO modification. Mutation of these sites significantly affects the transcriptional activity of MITF but does not alter dimerization, DNA binding, stability, or nuclear localization. Mutagenesis reducing the number of MITF binding sites in the promoter of TRPM1 from three to one eliminated the difference in transcriptional activity between the MITF mutants. Among other MITF target gene promoter constructs, differences in transcriptional activity between wild type and non-sumoylatable MITF were only seen in promoters with multiple MITF binding sites. These data support a synergy control model in which the functional consequences of MITF sumoylation depend on promoter context. Sumoylation, thus, provides a possible mechanism for altering the effects of MITF by affecting the target genes that it activates. MITF is a tissue-restricted, basic helix-loop-helix leucine zipper dimeric transcription factor. It is encoded by the mitf locus in mice (1Hodgkinson C.A. Moore K.J. Nakayama A. Steingrimsson E. Copeland N.G. Jenkins N.A. Arnheiter H. Cell. 1993; 74: 395-404Abstract Full Text PDF PubMed Scopus (950) Google Scholar) and when mutated leads to defects in melanocytes, the retinal pigment epithelium, mast cells, and osteosclasts. Mitf mutant mice are white due to a complete lack of melanocytes, whereas heterozygotes have a white belly spot (1Hodgkinson C.A. Moore K.J. Nakayama A. Steingrimsson E. Copeland N.G. Jenkins N.A. Arnheiter H. Cell. 1993; 74: 395-404Abstract Full Text PDF PubMed Scopus (950) Google Scholar, 2Silvers W.K. The Coat Colors of Mice: A Model for Mammalian Gene Action and Interaction. Springer-Verlag New York Inc., New York1979: 268-291Crossref Google Scholar), demonstrating a requirement for mitf in production of this lineage. MITF continues to be necessary in the adult based on the existence of hypomorphic alleles in mice which cause postnatal melanocyte death and premature graying (3Lerner A.B. Shiohara T. Boissy R.E. Jacobson K.A. Lamoreux M.L. Moellmann G.E. J. Investig. Dermatol. 1986; 87: 299-304Abstract Full Text PDF PubMed Scopus (110) Google Scholar, 4Steingrimsson E. Moore K.J. Lamoreux M.L. Ferre-D'Amare A.R. Burley S.K. Zimring D.C. Skow L.C. Hodgkinson C.A. Arnheiter H. Copeland N.G. Jenkins N.A. Nat. Genet. 1994; 8: 256-263Crossref PubMed Scopus (444) Google Scholar). As a transcriptional mediator of differentiation, MITF acts down-stream of the melanizing hormone α-melanocyte-stimulating hormone (5Price E.R. Horstmann M.A. Wells A.G. Weilbaecher K.N. Takemoto C.M. Landis M.W. Fisher D.E. J. Biol. Chem. 1998; 273: 33042-33047Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar) and transcriptionally regulates the expression of the enzymes necessary for melanin production in differentiated melanocytes (for review, see Ref. 6Goding C.R. Genes Dev. 2000; 14: 1712-1728PubMed Google Scholar). Although these data implicate MITF in both the survival and differentiation of melanocytes, little is known about biochemical regulatory pathways that control MITF in these different roles. MITF is part of the MiT transcription factor family whose members share significant homology and recognize the same DNA elements. Functionally, MITF binds to the canonical E-box promoter sequence CACGTG as well as to the non-palindromic sequence CACATG (7Hemesath T.J. Steingrimsson E. McGill G. Hansen M.J. Vaught J. Hodgkinson C.A. Arnheiter H. Copeland N.G. Jenkins N.A. Fisher D.E. Genes Dev. 1994; 8: 2770-2780Crossref PubMed Scopus (560) Google Scholar, 8Tachibana M. Perez-Jurado L.A. Nakayama A. Hodgkinson C.A. Li X. Schneider M. Miki T. Fex J. Francke U. Arnheiter H. Hum. Mol. Genet. 1994; 3: 553-557Crossref PubMed Scopus (175) Google Scholar). MITF functions as either a homodimer or as a heterodimer with the related MiT family transcription factors TFE3, TFEB, and TFEC (62Mansky K.C. Sulzbacher S. Purdom G. Nelsen L. Hume D.A. Rehli M. Ostrowski M.C. J. Leukocyte Biol. 2002; 71: 304-310PubMed Google Scholar). The related factor TFEB was recently identified as a translocated oncogene in papillary renal cell carcinoma in humans (10Davis I.J. Hsi B.L. Arroyo J.D. Vargas S.O. Yeh Y.A. Motyckova G. Valencia P. Perez-Atayde A.R. Argani P. Ladanyi M. Fletcher J.A. Fisher D.E. Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 6051-6056Crossref PubMed Scopus (228) Google Scholar, 11Kuiper R.P. Schepens M. Thijssen J. van den van Asseldonk M. Berg E. Bridge J. Schuuring E. Schoenmakers E.F. van Kessel A.G. Hum. Mol. Genet. 2003; 12: 1661-1669Crossref PubMed Scopus (175) Google Scholar). The structural features of these family members are so similar that MITF and TFE3 have been shown to genetically compensate for one another in regulation of osteoclast development in mice (12Steingrimsson E. Tessarollo L. Pathak B. Hou L. Arnheiter H. Copeland N.G. Jenkins N.A. Proc. Natl. Acad. Sci. U. S. A. 2002; PubMed Scopus Google Scholar). post-translational members of the MiT melanocytes, of the by leads to of MITF T.J. E.R. Takemoto T. Fisher D.E. 1998; PubMed Scopus Google Scholar), of the E.R. T. S. Takemoto T.J. Fisher D.E. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar) as well as and of MITF M. T.J. Takemoto C.M. Horstmann M.A. Wells A.G. E.R. Fisher Fisher D.E. Genes Dev. 2000; 14: Google Scholar). factor a in of both MITF and TFE3 a conserved of K.N. Motyckova G. Takemoto C.M. T.J. Wells A.G. Fisher D.E. Mol. Cell. 8: Full Text Full Text PDF PubMed Scopus Google Scholar). post-translational that have been shown or to MITF Takemoto A. Fisher D.E. M. Hum. Mol. Genet. 2000; PubMed Scopus Google Scholar) and by in K.C. U. J. Ostrowski M.C. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). MITF been shown to be by the of H. E. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, A. E. Mol. Cell. Biol. 2003; PubMed Scopus Google Scholar), a of the transcriptional that been in the of post-translational by SUMO small ubiquitin-like wild cells, and of of the and of H. 2002; PubMed Scopus Google Scholar, T. H. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, U. Mol. Cell. Biol. 2002; PubMed Scopus Google Scholar). is the post-translational of by the of the small (SUMO) (for review, see A. PubMed Scopus Google Scholar, M. 2000; PubMed Scopus Google Scholar, S. G. S. Nat. Mol. Biol. PubMed Scopus Google Scholar). is to lysine residues in a consensus sequence J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), a to The in this is the heterodimer J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), the is J. PubMed Scopus Google Scholar), and the enzymes members of the family M. Cell. Full Text Full Text PDF PubMed Scopus Google Scholar) or A. A. A. Cell. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). are the functional consequences of SUMO it with and Mol. Cell. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar), alter T. L. Cell. Full Text Full Text PDF PubMed Scopus Google Scholar, M.J. E. G. J. Biol. PubMed Scopus Google Scholar), to nuclear J. PubMed Scopus Google Scholar), or transcriptional activity J. G. J. PubMed Scopus Google Scholar, S. G. Mol. Cell. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, S. Proc. Natl. Acad. Sci. U. S. A. 2002; PubMed Scopus Google Scholar) (for review, see Ref. S. Cell. Mol. Sci. 2003; PubMed Scopus Google Scholar). transcription and the consensus for sumoylation been identified as part of a that regulates J.A. Mol. Cell. Biol. 2000; PubMed Scopus Google Scholar). of this transcriptional by SUMO in to the that sumoylation functions in synergy control J.A. Mol. Cell. Biol. 2000; PubMed Scopus Google Scholar, L. G. A. Mol. PubMed Scopus Google Scholar, S. J.A. Proc. Natl. Acad. Sci. U. S. A. 2003; 100: PubMed Scopus Google Scholar). this sumoylation of a transcription factor transcriptional activity promoters with multiple binding sites (for review, see Ref. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). one model of residues in a to the sumoylation consensus to transcriptional activity in the mutants. this was only on promoter that multiple S. J.A. Proc. Natl. Acad. Sci. U. S. A. 2003; 100: PubMed Scopus Google Scholar). similar but that this on synergy with sumoylation the lysine within the synergy control L. J.A. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). of the MITF sequence the of conserved sumoylation consensus sites in the and MITF been shown to with L. J. Yeh 2000; PubMed Scopus Google Scholar) and H. E. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, A. E. Mol. Cell. Biol. 2003; PubMed Scopus Google Scholar), of the sumoylation MITF is a for MITF was to be subject to SUMO as were the related family members TFE3 and affecting sumoylation significant functional consequences on transcriptional activity of which not to dimerization, DNA binding, stability, or nuclear localization. was that the difference in transcriptional activity the MITF on the number of MITF binding sites within the a synergy control model J.A. Mol. Cell. Biol. 2000; PubMed Scopus Google Scholar, S. J.A. Proc. Natl. Acad. Sci. U. S. A. 2003; 100: PubMed Scopus Google Scholar, L. J.A. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). These sumoylation as a post-translational MITF that affects MITF transcriptional activity in a on the promoter in MITF target MITF and have been J. S. Fisher D.E. PubMed Scopus Google Scholar). of MITF were the the with The TFE3 was from from from and with the and The TFE3 was with and with the same and the was J. I.J. M. Fisher D.E. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar) the and sites. a TFEB, was from papillary renal cell carcinoma cell transcription with A the of TFEB was by a that and sequence expression of the and for TFEB, The was by with a for the of of TFEB, and The were and were by with and or and the and sites of was a of and been S. S. A. P. Mol. Cell. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). was by and is a of the of by of and sites and and with and sites and The and wild type MITF were and the and sites of to was from a melanocyte to and and The was been H. E. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). The J. S. Fisher D.E. PubMed Scopus Google Scholar), promoter J. Horstmann M.A. S. Fisher D.E. J. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar), G. Weilbaecher K.N. Horstmann M. Fisher Fisher D.E. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar), and promoter T. C.R. Mol. Cell. Biol. 1994; 14: PubMed Scopus Google Scholar) have been The been H. PubMed Scopus Google Scholar). or expression were a from were by in were with of and of or of cell to the were for and of each were were for by to control cell and were in with and to the were were with the of or of control and the of wild type or mutant or of DNA were in as were in for and was for the activity was to the and were on three and or in were with the of were cell were by in by in in and and was to T. Cell. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). were for with in by in a to and by of were by of with by in with and in and were for with by on in in with a to and by of were by of with by in with and in were by in or and to from were and to MITF or were as M. T.J. Takemoto C.M. Horstmann M.A. Wells A.G. E.R. Fisher Fisher D.E. Genes Dev. 2000; 14: Google Scholar) from with or MITF or were as J. S. Fisher D.E. PubMed Scopus Google Scholar). or were in and with of MITF and of to the were in were for with in in and for with in were in for for in with and with in were in for and with in were in with in for and was a a and was with a and MITF and or were in with of wild type and of of and of or of and of to the were a were with for the of the in were with of wild type or and of were and were as MITF by in the melanocyte of MITF and were in cells, were of and in to the of MITF to by T.J. E.R. Takemoto T. Fisher D.E. 1998; PubMed Scopus Google seen not were in and these were these not the of which is the of these of that these from the of which be and which been to SUMO T. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, G. M.A. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). MITF and the same of MITF as seen in were in of and in that this of the and and were in the from and when were by with and wild type MITF were by for MITF were seen in not the of SUMO of MITF of We to on MITF in We in by in and as T. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). this of MITF that be with of the and of MITF were by to expression and of known to these T.J. E.R. Takemoto T. Fisher D.E. 1998; PubMed Scopus Google Scholar, E.R. T. S. Takemoto T.J. Fisher D.E. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar, K.N. Motyckova G. Takemoto C.M. T.J. Wells A.G. Fisher D.E. Mol. Cell. 8: Full Text Full Text PDF PubMed Scopus Google Scholar). to the and of MITF are as and which that be with SUMO modification. these were identified only with to the other modifications. to SUMO were due to of to of cell were and for expression not of for MITF MITF similar as in with and and which are of the A in the cell is with the that MITF is subject to SUMO within of the of and MITF the of conserved consensus sites J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) and in the and were by residues to these were in with wild type only one was seen in with MITF mutated either or Mutation of both the of MITF SUMO to these of SUMO that is the on MiT by of MITF and its related family TFEB and TFE3, of one similar to the of TFE3 the to in whereas TFEB the to in MITF of or in with that of both MiT family members are by of and As of TFEB and TFE3 a as was not a as was for for the wild type MITF or the non-sumoylatable mutant with TFEB or TFE3 to sumoylation was for with these other family both wild type or mutant MITF was of either TFE3 or TFEB of to either TFE3 or TFEB and of with of similar of wild type MITF or MITF not MITF of the family of been to as in the (for review, see U. Mol. Cell. Biol. 2002; PubMed Scopus Google and Genes Dev. PubMed Scopus Google Scholar). It been recently that with MITF H. E. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, A. E. Mol. Cell. Biol. 2003; PubMed Scopus Google Scholar) and its transcriptional We by expression J. J. E. and E. that and are in cell not expression of and in a of cell not the either was of to As seen in only MITF sumoylation as and in the of MITF that been both sumoylation sites to a of by in of MITF different one sumoylation or both sites. of the of MITF in the and of that MITF sumoylation when either or was that is of sumoylation either of on MITF of been shown to MITF transcription in H. E. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). this be due to of MITF of or MITF in of or with MITF to a significant in similar with the MITF the was or of sumoylation not transcriptional effects have been for other family members S. Proc. Natl. Acad. Sci. U. S. A. 2002; PubMed Scopus Google Scholar, S. L. H. A. Genes Dev. PubMed Scopus Google Scholar), and for SUMO have been shown S. Proc. Natl. Acad. Sci. U. S. A. 2002; PubMed Scopus Google Scholar). A number of are known to be or to with family members transcription transcriptional U. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar), and A. A. S. E. M. A. T. A. J. 2002; PubMed Scopus Google Scholar). it been that of or family members leads to a of a of the sumoylation of a transcription factor L. J.A. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). of or to the of MITF the effects of sumoylation by MITF a that been for other transcription factors S. G. Mol. Cell. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, E. Mol. Cell. 2003; 12: Full Text Full Text PDF PubMed Scopus Google Scholar). These wild type MITF and in the SUMO sites and as well as a of to the its which by The activity of wild type MITF and that lack either or both sites were in in which lack MITF The recently promoter of J. S. Fisher D.E. PubMed Scopus Google Scholar) was the of MITF and wild type MITF this promoter MITF either this promoter whereas MITF mutant the promoter about wild type with wild type the the promoter but is of effects were seen in not this difference in activity a of affects the MITF of a promoter with multiple MITF binding were with of the TRPM1 promoter which three MITF binding and of control of MITF wild MITF or were with the of DNA by the of the same were with the promoter in which MITF binding sites were mutated by data from A and shown as to were with of the promoter which one MITF binding of control and of MITF wild MITF or are shown as to were as in with the promoter which MITF binding sites. were as in with the which MITF binding of to MITF DNA to the of the to transcription was due to a in DNA a a MITF consensus E-box from the TRPM1 promoter J. S. Fisher D.E. PubMed Scopus Google Scholar), wild type MITF and this DNA MITF and were in from which nuclear of MITF in were by not and similar of MITF were for It is that the SUMO DNA binding it The of this show that each of these the to this that both the MITF and are of MITF for DNA binding (7Hemesath T.J. Steingrimsson E. McGill G. Hansen M.J. Vaught J. Hodgkinson C.A. Arnheiter H. Copeland N.G. Jenkins N.A. Fisher D.E. Genes Dev. 1994; 8: 2770-2780Crossref PubMed Scopus (560) Google Scholar). of MITF possible for the different transcriptional of MITF wild MITF and the be nuclear or be related to nuclear A. A. A. Cell. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar) and control the of in S. S. A. P. Mol. Cell. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, T. H. J. Biol. PubMed Scopus Google Scholar). of with wild type MITF and of each to the We not of wild type or the nuclear that are of the the of to the in the same as wild that this on nuclear of on MITF been to of Mol. Cell. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar) and to have effects on Although expression of wild type MITF and mutant were similar in the activity of the MITF mutant be due to its by of MITF was shown to MITF and M. T.J. Takemoto C.M. Horstmann M.A. Wells A.G. E.R. Fisher Fisher D.E. Genes Dev. 2000; 14: Google Scholar, L. J. Yeh 2000; PubMed Scopus Google Scholar). We the of sumoylation on MITF expression in by with which leads to MITF and M. T.J. Takemoto C.M. Horstmann M.A. Wells A.G. E.R. Fisher Fisher D.E. Genes Dev. 2000; 14: Google Scholar). were in the of to and of to MITF MITF differences were for either MITF or MITF of with MITF on the of wild type MITF not These data that sumoylation does not the of MITF that MITF the of these that of MITF by was not with a significant in the of MITF sumoylation not We of the sites affects the of type and were with in cells, and were by differences were in the of wild type or mutant MITF by this not These data that does not MITF are the for MITF and MITF the TRPM1 promoter which three MITF binding and a mutant in which of the sites have been by J. S. Fisher D.E. PubMed Scopus Google Scholar), the between multiple MITF binding sites and MITF cells, which not MITF from to with of either of to this that MITF was wild type MITF on the promoter but difference in activity on the mutant promoter MITF A and that the activity on the wild type but in the of the the was as as either wild type or MITF A and As in the differences in activity between the MITF only in the of the promoter with multiple MITF binding sites. These data that sumoylation the of multiple MITF binding sites in a promoter We this a of other the T. C.R. Mol. Cell. Biol. 1994; 14: PubMed Scopus Google Scholar), J. Horstmann M.A. S. Fisher D.E. J. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar), and G. Weilbaecher K.N. Horstmann M. Fisher Fisher D.E. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). the sumoylation of MITF only affects MITF transcriptional activity when multiple are it be that the of MITF MITF and be on promoters with one E-box as whereas the activity on promoters with multiple as and the same as have this to be the and both and MITF was wild type whereas the was the of wild type MITF and were when the promoter for which a MITF binding of have identified MITF as a and have the sites to consensus in We have that this in in a cell as well as data from a cell to that of of the related MiT family TFEB and TFE3, a sumoylation and have shown that these are that the effects of sumoylation on MITF be for these other family The of this members of this transcription factor family that it be for regulation of of the MiT family of MITF affects its transcriptional but this difference the of multiple MITF binding sites in the promoters of target provides a possible mechanism for the target gene of which be in the of MITF in differentiation and The of the differences in transcriptional activity between wild type MITF and the non-sumoylatable mutant are not but are of a the basic helix-loop-helix leucine zipper which the MITF as well as the it is well that transcriptional in as to effects that are of be MITF transcriptional of which was genetically in of was seen to only a difference when in Horstmann M. J. Motyckova G. S. I.J. Fisher D.E. Cell. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). the transcriptional differences of transcriptional target genes which are the of synergy control be to significantly to the of the for transcription factors as which are to the differentiation of the melanocyte lineage. of have shown that is of MITF sumoylation in and within SUMO consensus sites. Mutation of these residues sumoylation and leads to transcriptional that the of MITF transcriptional activity by H. E. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar, A. E. Mol. Cell. Biol. 2003; PubMed Scopus Google Scholar) be due to its as SUMO the of or both to to transcriptional effects that were not to MITF and to it been that binds to MITF H. E. J. Biol. Chem. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar), it possible that of it been recently that of sumoylation M. PubMed Scopus Google Scholar). We to possible of the of of in a of of the in MITF and to to transcriptional activity of the mutant MITF was significantly wild to the mechanism of this that this not of MiT family members it the nuclear of MITF or MITF and in the the difference in transcriptional activity only on a promoter with multiple MITF binding sites. of the a mutant with a MITF binding the difference in transcriptional activity between wild type MITF and MITF on the it that only a small of is in these It be to the between MITF and MITF transcriptional activity in the a of MITF for activity of its a with or or in not be well in activity be by the of MITF activity by of SUMO to MITF does sumoylation and does of as by its DNA of in promoters multiple binding sites for this transcription factor. to a synergy control SUMO the expression of MITF target the expression of target genes as TRPM1 but does not target genes by a MITF binding as of the to as α-melanocyte-stimulating hormone that the transcription of MITF sumoylation to a of promoters with multiple binding the of MITF to promoters with elements. of sumoylation MITF to on promoters with multiple binding sites and to a in sumoylation of MITF be control of the of target genes in the MITF a mechanism be for it to have significantly different in that control of melanocyte and control of melanocyte As the of MITF transcriptional to it be possible to the to which as synergy control by sumoylation to the of effects by the expression of related family as TFEB and TFE3, in transcriptional target that be by post-translational is the which SUMO is sumoylation of MITF a or a or the The of SUMO to the of MITF not its to to the or transcriptionally a promoter with a MITF binding transcriptional activity on a promoter with multiple MITF binding sites be due to in It been that SUMO affects synergy control by to promoters L. J.A. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). the of SUMO in the which SUMO to the of We the members of the Fisher for and Motyckova the TFE3 and with We and for this

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