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Mammalian skeletal muscles are a mosaic of different fiber types largely defined by differential myosin heavy chain (MyHC) expression. Little is known about the molecular mechanisms regulating expression of the MyHC gene family members in different fiber types. In this work, we identified several cis- and trans-elements that regulate expression of the three adult fast MyHC genes. Despite multiple DNA-binding motifs for well characterized muscle transcription factors upstream of all three fast MyHC genes, expression of MyoD/Myf-5, calcineurin, or NFAT3 had different effects on the three promoters. MyoD or Myf-5 overexpression preferentially activated the IIb promoter, whereas NFAT or activated calcineurin overexpression preferentially activated the IIa promoter. Calcineurin had a 50–100-fold stimulatory effect on the IIa promoter, and the known downstream effectors of calcineurin (myocyte enhancer factor-2 and NFAT) cannot completely account for this activation. Finally, we identified two elements critical for regulating MyHC-IId/x expression: a 130-base pair enhancer element and a CArG-like element that inhibited IId/x promoter activity in vitro. Thus, we have found specific regulatory pathways that are distinct for the three adult fast MyHC genes. These elements are logical candidates for fiber-specific control of skeletal muscle gene expression in vivo. Mammalian skeletal muscles are a mosaic of different fiber types largely defined by differential myosin heavy chain (MyHC) expression. Little is known about the molecular mechanisms regulating expression of the MyHC gene family members in different fiber types. In this work, we identified several cis- and trans-elements that regulate expression of the three adult fast MyHC genes. Despite multiple DNA-binding motifs for well characterized muscle transcription factors upstream of all three fast MyHC genes, expression of MyoD/Myf-5, calcineurin, or NFAT3 had different effects on the three promoters. MyoD or Myf-5 overexpression preferentially activated the IIb promoter, whereas NFAT or activated calcineurin overexpression preferentially activated the IIa promoter. Calcineurin had a 50–100-fold stimulatory effect on the IIa promoter, and the known downstream effectors of calcineurin (myocyte enhancer factor-2 and NFAT) cannot completely account for this activation. Finally, we identified two elements critical for regulating MyHC-IId/x expression: a 130-base pair enhancer element and a CArG-like element that inhibited IId/x promoter activity in vitro. Thus, we have found specific regulatory pathways that are distinct for the three adult fast MyHC genes. These elements are logical candidates for fiber-specific control of skeletal muscle gene expression in vivo. myosin heavy chain myogenic regulatory factor serum response factor myocyte enhancer factor-2 kilobase(s) cytomegalovirus base pair(s) The sarcomeric myosin heavy chain (MyHC)1 gene family consists of eight known isoforms, each encoded by separate genes exhibiting a complex pattern of spatial and temporal regulation (1Weiss A. Leinwand L.A. Annu. Rev. Cell Dev. Biol. 1996; 12: 417-439Crossref PubMed Scopus (280) Google Scholar). Of the eight isoforms, four are expressed in adult skeletal muscle: type I or slow MyHC and three fast isoforms, IIa, IId/x, and IIb. Greater than 90% of the MyHC in adult skeletal muscle is composed of these latter three gene products. The three adult fast MyHC isoforms are expressed in different types of skeletal muscle fibers that have different physiological characteristics, with IIA fibers being smaller, slower, and more oxidative; IIB fibers typically being the largest, fastest, and most glycolytic; and IID/X fibers falling between these extremes (2Talmadge R.J. Roy R.R. Edgerton V.R. Curr. Opin. Rheumatol. 1993; 5: 695-705Crossref PubMed Scopus (56) Google Scholar). A greater understanding of the mechanisms regulating MyHC gene transcription would provide tremendous insights into how these individual fiber types are established and maintained. Several axes of regulation exist for the members of the MyHC gene family, including tissue-specific (muscle versusnon-muscle), muscle type-specific (striated versus smooth muscle), fiber type-specific (fast versus slow), and fiber subtype-specific (fast IIa versus IId/x versusIIb). Many of these regulatory decisions are likely to be determined by different transcription factor-binding motifs within the upstream promoter regions of the different MyHC genes. For example, the adult fast MyHC-IIa, -IId/x, and -IIb genes undoubtedly share similar pathways for conferring muscle-specific and fast fiber-specific expression; but because they are expressed in distinct fiber subtypes (IIA, IID/X, and IIB), they must also have unique regulatory circuits as well. However, because there are no data directly comparing the sequence or physiological regulation of the three adult fast MyHC gene regulatory regions, nothing is known about the mechanisms that regulate the differential expression of these genes in distinct fast fiber subtypes. Of the three adult skeletal fast MyHC genes, only the promoter region of the mouse MyHC-IIb gene has been analyzed to date (11Diagana T.T. North D.L. Jabet C. Fiszman M.Y. Takeda S. Whalen R.G. J. Mol. Biol. 1997; 265: 480-493Crossref PubMed Scopus (18) Google Scholar, 12Lakich M.M. Diagana T.T. North D.L. Whalen R.G. J. Biol. Chem. 1998; 273: 15217-15226Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 13Swoap S.J. Am. J. Physiol. 1998; 274: C681-C687Crossref PubMed Google Scholar, 14Takeda S. North D.L. Lakich M.M. Russell S.D. Whalen R.G. J. Biol. Chem. 1992; 267: 16957-16967Abstract Full Text PDF PubMed Google Scholar, 15Takeda S. North D.L. Diagana T. Miyagoe Y. Lakich M.M. Whalen R.G. J. Biol. Chem. 1995; 270: 15664-15670Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 16Wheeler M.T. Snyder E.C. Patterson M.N. Swoap S.J. Am. J. Physiol. 1999; 276: C1069-C1078Crossref PubMed Google Scholar). Several muscle-specific regulatory elements have been found within the proximal IIb promoter, including potential binding sites for the myogenic regulatory factors (MRFs), serum response factor (SRF), and myocyte enhancer factor-2 (MEF-2) (11Diagana T.T. North D.L. Jabet C. Fiszman M.Y. Takeda S. Whalen R.G. J. Mol. Biol. 1997; 265: 480-493Crossref PubMed Scopus (18) Google Scholar, 12Lakich M.M. Diagana T.T. North D.L. Whalen R.G. J. Biol. Chem. 1998; 273: 15217-15226Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 13Swoap S.J. Am. J. Physiol. 1998; 274: C681-C687Crossref PubMed Google Scholar, 14Takeda S. North D.L. Lakich M.M. Russell S.D. Whalen R.G. J. Biol. Chem. 1992; 267: 16957-16967Abstract Full Text PDF PubMed Google Scholar, 15Takeda S. North D.L. Diagana T. Miyagoe Y. Lakich M.M. Whalen R.G. J. Biol. Chem. 1995; 270: 15664-15670Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 16Wheeler M.T. Snyder E.C. Patterson M.N. Swoap S.J. Am. J. Physiol. 1999; 276: C1069-C1078Crossref PubMed Google Scholar). Overexpression of any of the four MRFs greatly increases IIb promoter construct activity in differentiated C2C12 myotubes (15Takeda S. North D.L. Diagana T. Miyagoe Y. Lakich M.M. Whalen R.G. J. Biol. Chem. 1995; 270: 15664-15670Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar), whereas gene transfer studies have demonstrated that an E-box just upstream of the transcription start site is for expression of the IIb gene in M.T. Snyder E.C. Patterson M.N. Swoap S.J. Am. J. Physiol. 1999; 276: C1069-C1078Crossref PubMed Google Scholar). In of the proximal element binding and greatly promoter activity M.M. Diagana T.T. North D.L. Whalen R.G. J. Biol. Chem. 1998; 273: 15217-15226Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar). These studies have established that members of the and of myogenic transcription factors to be for muscle-specific expression of the MyHC-IIb has been in the sites that to slow versus fast muscle gene expression. that to a in slow fiber-specific gene expression is the calcineurin C. Dev. 1998; 12: PubMed Scopus Google Scholar, J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). Calcineurin is a that and of the NFAT factor of transcription factors C. Dev. 1998; 12: PubMed Scopus Google Scholar). NFAT to and the slow fiber-specific gene C. Dev. 1998; 12: PubMed Scopus Google Scholar). A also transcription factors in slow fiber-specific gene expression T. J. A. and S. J. Scholar). including the T. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus (44) Google and the and of regulatory elements S. J. A. Mol. Biol. 1999; PubMed Scopus Google Scholar, J. J. S. A. Mol. Biol. 1996; PubMed Scopus Google Scholar), have also been in slow versus fast fiber gene expression. However, the of these elements has been largely with to the MyHC gene Thus, a of has been on the of muscle-specific transcription factors and on the factors slow versus fast fiber gene expression. there have been no data on the regulation of fiber-specific gene expression within the and IIB fast fiber subtypes. members of the MyHC family are the only genes to date that have distinct fast fiber isoforms, muscle-specific genes a in expression between different fast fiber subtypes J. 5: PubMed Scopus Google Scholar, S. C. Physiol. Rev. 1996; PubMed Scopus Google Scholar). the factors regulating the differential expression of the three adult fast MyHC genes provide insights into the of different fiber types. The of this to and the of the upstream promoter regions of the three adult fast MyHC genes and to to the factors for differential expression. have the upstream regulatory regions of the mouse MyHC-IIa, and genes and that is to muscle-specific expression in vitro. the differential of activity in IIb and the expression to the expression pattern of the MyHC genes. have identified several cis- and elements with distinct effects on each of the adult fast MyHC promoter regions that a in fiber-specific gene expression in vivo. of mouse MyHC gene C. Leinwand J. Cell Biol. 1997; PubMed Scopus Google Scholar). each of the mouse and MyHC-IId/x promoter in the and The cytomegalovirus as a for all The promoter by and and MyHC sites on each of the three adult fast promoters. to MyHC-IIb to and MyHC-IId/x to the of all three promoter than we in with of each promoter to a promoter and for of these be to as the The promoter by chain the type IIa, and IId/x as and with The expression a of the expression a of and the and calcineurin expression all by for by C2C12 and on in with and serum with of and of to the In all of a construct as an a the and with serum or and myotubes For a of of of MyHC and of a control or of the expression A in and of the for promoter and and a are as by For and and myotubes into myosin Whalen R.G. Dev. Biol. PubMed Scopus Google and on for for to the the determined the and to to separate the different isoforms as by and Roy R.J. Roy R.R. J. Physiol. 1993; PubMed Scopus Google Scholar). to a transfer and for MyHC an that all skeletal isoforms of MyHC J. Biol. Chem. Full Text PDF PubMed Google Scholar). A that the upstream regulatory regions of the mouse MyHC-IIa, and share within the proximal The between the proximal is as IIa and in IId/x and in and IIa and IId/x, in The for all three genes is within the proximal the the to The proximal of the mouse adult fast MyHC share four elements within the of upstream promoter sequence the sequence is in all three fast MyHC and is to the sequence for J. J. J. Biol. Chem. Full Text PDF PubMed Google Scholar, J. Biol. Chem. Full Text PDF PubMed Google Scholar). The gene a that to be the in mouse as several with this start site a is found in all three in the IIb promoter, a in there are base pair in the and MyHC-IId/x genes that likely binding S. PubMed Scopus Google Scholar, T. Mol. Biol. PubMed Scopus Google Scholar, Dev. PubMed Scopus Google Scholar, T. PubMed Google Scholar, Mol. Biol. PubMed Scopus Google Scholar). the and the are all three fast MyHC genes The is a region by Lakich M.M. Diagana T.T. North D.L. Whalen R.G. J. Biol. Chem. 1998; 273: 15217-15226Abstract Full Text Full Text PDF PubMed Scopus (44) Google that is in all three fast MyHC genes proximal element a binding site for to be critical in expression of the MyHC-IIb promoter M.M. Diagana T.T. North D.L. Whalen R.G. J. Biol. Chem. 1998; 273: 15217-15226Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 13Swoap S.J. Am. J. Physiol. 1998; 274: C681-C687Crossref PubMed Google Scholar). Finally, a region is also all three fast MyHC genes, with IIb and IId/x of and IIa and IIb of In to the CArG-like and regions the upstream promoter regions of the MyHC-IIa, and genes also several potential sites for NFAT and binding are two in the proximal promoter, in the IId/x promoter, and two in the IIb promoter are three sites in the IIa promoter, in the IId/x promoter, and two in the IIb promoter for the of the T. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus (44) Google and for the and elements S. J. A. Mol. Biol. 1999; PubMed Scopus Google J. J. S. A. Mol. Biol. 1996; PubMed Scopus Google to any in any of the three adult fast MyHC genes of all three adult fast MyHC in C2C12 and in differentiated promoter activity by for the IIb promoter, by for the IId/x promoter, and by for the IIa promoter in that of the three adult fast MyHC is to muscle-specific expression and expression in vitro. activity in myotubes different the three adult fast with IId/x the by IIb and IIa in differentiated the IId/x the most expressed adult of adult fast by IIb and IIa These data that the adult fast MyHC differential activity that is with the expression pattern of the MyHC genes in C2C12 the region is in the three mouse adult fast MyHC genes this sequence for all three fast MyHC of all three fast MyHC promoter to a similar by of the region that this element is in the differential expression of the adult fast MyHC genes, but that a in the expression of all three genes. of the region in expression in that is for of muscle-specific expression element found in all three adult fast is the CArG-like element of this element in the of the promoter in a in expression of the IIa promoter, whereas IIb promoter activity of the CArG-like element the IId/x promoter in a in IId/x promoter activity Thus, the CArG-like element has differential effects on MyHC promoter for IIa, is an for has no and for IId/x, is studies have that the activity of the IIb promoter is to overexpression (15Takeda S. North D.L. Diagana T. Miyagoe Y. Lakich M.M. Whalen R.G. J. Biol. Chem. 1995; 270: 15664-15670Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 16Wheeler M.T. Snyder E.C. Patterson M.N. Swoap S.J. Am. J. Physiol. 1999; 276: C1069-C1078Crossref PubMed Google Scholar). In C2C12 the IIb promoter region as for of the IIb promoter by Takeda (15Takeda S. North D.L. Diagana T. Miyagoe Y. Lakich M.M. Whalen R.G. J. Biol. Chem. 1995; 270: 15664-15670Abstract Full Text Full Text PDF PubMed Scopus (34) Google activity by overexpression of MyoD and by overexpression of Myf-5 as a of MyoD IIb promoter activity that greater than IIa or promoter activity In with MyoD or Myf-5 had no effect on the activity of the or MyHC-IId/x promoter the of multiple in each promoter. with a in a in expression of the IIb promoter and no in the of the IIa and IId/x Thus, IIb is the only promoter to overexpression of all three of MyHC-IIa, and promoter in response to MyoD or calcineurin different different different different different different are four to different The data MyoD and calcineurin are different different is the control are different different in a are four to different The data MyoD and calcineurin are different different is the control are has a for the in slow versus fast fiber gene expression C. Dev. 1998; 12: PubMed Scopus Google Scholar, J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the three adult fast MyHC genes, the to fast is IId/x, and IIa, with IIa being expressed in the most fast the that the IIa promoter would be more to calcineurin or NFAT with the IIb and IId/x promoters. with a calcineurin expression in a greater of IIa promoter activity with IIb or IId/x promoter calcineurin IIa promoter activity by but IIb and IId/x promoter by only The in IIa promoter activity in IIa promoter activity that greater than that of IIb and different that of in response to calcineurin with a NFAT expression in a of expression of IIa with IIb or IId/x promoter IIa promoter activity by by whereas NFAT overexpression in a in IIb and IId/x promoter Finally, with an expression construct in a of the IIa promoter, but only IIb or but because the effect on IIa the that the and have differential effects on adult fast MyHC promoter activity in muscle However, the effect of a be by the of expressed in muscle that or the effects of overexpression of MyoD and activated calcineurin on adult fast MyHC promoter activity in a be expressed in muscle that overexpression an effect on promoter we have an construct C. 1999; PubMed Google Scholar), that activity is in C2C12 myotubes we the effects of overexpression on adult fast MyHC promoter activity in as well. Overexpression of activated calcineurin the differential effects in as in C2C12 with IIa IId/x the of the response than in C2C12 myotubes Overexpression of MyoD the of all three adult fast overexpression of MyoD in MyHC-IIb promoter activity to a greater than IIa or IId/x promoter activity Overexpression of in the of all three adult fast MyHC by These data the that MyoD and calcineurin have differential effects on the adult fast MyHC whereas has more or effects on expression. calcineurin is to the NFAT and of transcription factors to effect on gene expression C. Dev. 1998; 12: PubMed Scopus Google Scholar, J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), we the effects of calcineurin on promoter or of the and of the proximal region or of the proximal NFAT site in the IIa promoter in a in the calcineurin of the IIa promoter of elements in a in IIa promoter to calcineurin to a of that of the IIa construct The of the IIa with the the NFAT or different the activity of the control of the proximal site within the of a IIa promoter the calcineurin to of that of the construct However, this construct with a NFAT site a in IIa promoter activity in response to Finally, calcineurin only expression of the control to of upstream promoter sequence would or the differential pattern of expression of the three adult fast MyHC promoters. of the IIa promoter construct to had only effects on IIa promoter but to in an in promoter activity For the IId/x promoter to in a in promoter but to in an in IId/x promoter activity to different of the promoter. to IId/x promoter activity by whereas to IId/x promoter activity of the IIb construct to in a in IIb promoter to in a in promoter activity to to of the construct to of upstream promoter expression with the IIb promoter to in a in expression of any of the adult fast and the expressed in that muscle-specific expression maintained. In the region between and to elements for and differential muscle expression of all three adult fast MyHC whereas the conferring muscle-specific expression within the proximal region of the three adult skeletal fast of the region in the MyHC-IId/x promoter. of the promoter region in a in IId/x promoter within this region demonstrated that of any region within this in a in IId/x promoter in a in IId/x promoter the region of the IId/x promoter as an enhancer element in a of of this region to the promoter of the MyHC-IIb promoter in a in IIb promoter of two in a in IIb promoter The that to of the MyHC-IId/x promoter in a in MyHC-IId/x promoter activity to a region identified by to that has between the mouse and MyHC-IId/x this region in the IId/x promoter, activity by with the construct of of the IId/x region to a MyHC-IIb promoter in a in IIb promoter activity of two of this IId/x in an in IIb promoter Thus, the region of the IId/x promoter is and to expression on a promoter construct in vitro. four within this region to specific for this four had effects on MyHC-IId/x promoter of the of this region in of MyHC-IId/x promoter by In the studies have the elements regulating expression of individual members of the MyHC gene The upstream promoter regions of the and have been characterized in and in S. A. PubMed Scopus Google Scholar, J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar, J. Biol. Chem. Full Text PDF PubMed Google Scholar, A. Leinwand L.A. 1992; PubMed Google Scholar, S. J. J. J. Biol. Chem. Full Text PDF PubMed Google Scholar, J. S. J. J. J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar, A. J. S. J. J. J. Biol. Chem. Full Text PDF PubMed Google Scholar, Mol. Biol. PubMed Scopus Google Scholar), as has the promoter region of the adult skeletal fast MyHC-IIb gene (11Diagana T.T. North D.L. Jabet C. Fiszman M.Y. Takeda S. Whalen R.G. J. Mol. Biol. 1997; 265: 480-493Crossref PubMed Scopus (18) Google Scholar, 12Lakich M.M. Diagana T.T. North D.L. Whalen R.G. J. Biol. Chem. 1998; 273: 15217-15226Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 13Swoap S.J. Am. J. Physiol. 1998; 274: C681-C687Crossref PubMed Google Scholar, 14Takeda S. North D.L. Lakich M.M. Russell S.D. Whalen R.G. J. Biol. Chem. 1992; 267: 16957-16967Abstract Full Text PDF PubMed Google Scholar, 15Takeda S. North D.L. Diagana T. Miyagoe Y. Lakich M.M. Whalen R.G. J. Biol. Chem. 1995; 270: 15664-15670Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 16Wheeler M.T. Snyder E.C. Patterson M.N. Swoap S.J. Am. J. Physiol. 1999; 276: C1069-C1078Crossref PubMed Google Scholar). In cis- and elements have been identified that are for muscle-specific and fast versus slow fiber-specific gene expression. these studies have insights into the regulation of individual MyHC genes, there have been no data to date that have directly the promoter or the of the different MyHC in the physiological a is the elements conferring the in expression of the adult fast MyHC genes are to be In this we and the upstream promoter regions of the mouse and MyHC-IId/x genes with the characterized mouse MyHC-IIb gene S. North D.L. Lakich M.M. Russell S.D. Whalen R.G. J. Biol. Chem. 1992; 267: 16957-16967Abstract Full Text PDF PubMed Google Scholar), have the data directly comparing the and of these promoter regions in vitro. These data provide the for the regulatory circuits conferring differential expression of these three genes in distinct muscle fiber types and conferring to different physiological as muscle and in vivo. a to these complex in we have to the elements to and distinct for each adult skeletal fast MyHC to the expression pattern of the three adult fast MyHC in muscle and types in and to to specific cis- and elements that differential expression of the three adult fast MyHC genes. of the of of each of the MyHC in and that this of promoter region to muscle-specific expression; the of all three greater in differentiated C2C12 myotubes than in and differential expression of the three adult skeletal muscle in C2C12 myotubes in the IId/x IIb IIa, with the MyHC expression pattern in these these the that of upstream promoter the regulatory to and differential expression of the three adult skeletal fast MyHC genes in vitro. Several elements are in the proximal promoter regions of the three adult fast MyHC upstream promoter in is the in all three MyHC upstream promoter that of all three fast MyHC genes, but is found in members of the MyHC gene is to that be in conferring fast fiber-specific expression of the MyHC genes. of this element in the of the in a and in expression of all three fast MyHC in with the that this element is for expression of all three adult fast in vitro. element to members of the family of transcription factors M.M. Diagana T.T. North D.L. Whalen R.G. J. Biol. Chem. 1998; 273: 15217-15226Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar). Overexpression of in an in promoter activity for all three adult fast MyHC into of to this element be critical to the of fast fiber-specific expression of all three MyHC genes. However, of several fast muscle promoter regions, including muscle fast and myosin to any this sequence the MyHC genes this region is for fast fiber-specific MyHC gene fast fiber-specific genes to share this element that is is the CArG-like element in all three adult fast MyHC For this sequence is a for binding of has been in muscle-specific gene expression S. J. J. J. Biol. Chem. Full Text PDF PubMed Google Scholar). that of this element would have a effect on IIb promoter activity with IIa or IId/x promoter the IIb promoter the by of this activity whereas the activity of the IIa promoter by and that of the IId/x promoter by the IIa and IId/x base pair that greatly or binding S. PubMed Scopus Google Scholar, T. Mol. Biol. PubMed Scopus Google Scholar, Dev. PubMed Scopus Google Scholar, T. PubMed Google Scholar, Mol. Biol. PubMed Scopus Google Scholar). these data that is in this and that transcription factor is binding in this region and differential effects on MyHC gene expression. The differential effect on IIa expression that this element and binding be in MyHC-IId/x expression in IIA The the three adult fast MyHC upstream and downstream of the CArG-like A demonstrated that the of the response element are critical for conferring the specific effects of this element C. 1999; PubMed Google Scholar). these regions also in this is that they a in the of this of upstream promoter also to differential to MRFs and with a MyoD or Myf-5 overexpression construct MyHC-IIb promoter but IIa or IId/x promoter activity MyoD IIb promoter activity that greater than IIa or promoter activity effect on the IIb promoter that sequence of the IId/x promoter potential with two for the IIa promoter and two for the IIb promoter. Thus, the of potential sites the of these to the family with an activated of calcineurin in an in the of all three fast MyHC but the effect most on the IIa promoter, with a type IIA fibers typically are to slow type I fibers in and is that the gene is more to a slow fiber-specific also a for the and proximal sites in conferring calcineurin of the promoter, with of these elements the IIa promoter to calcineurin Thus, the and sites cannot completely account for the of IIa promoter activity by the differential of the three adult fast MyHC to and calcineurin we have also a effect of these factors on MyHC expression that MyoD overexpression in a in MyHC-IIb whereas calcineurin overexpression in a in expression. and A. these data that the between these two pathways a in the fiber-specific expression of the three adult fast MyHC genes. to between and in a in the differential expression pattern of the three adult skeletal fast MyHC in vitro. These data the that elements between and are for conferring and differential expression in muscle that this would two NFAT sites and two in the IIa promoter, two NFAT sites in the IIb promoter, and four NFAT sites and in the IId/x promoter. the differential of the three adult fast to members of these two transcription factor is that the of these sites for the of differential is that as regulatory pathways are also in the IId/x promoter that the region between and is for the activity of this promoter in region with that is between the mouse and IId/x of this region in a in IId/x promoter activity with the construct in with the data of this region of the IId/x promoter to the IIb promoter in a in promoter these data that this region is and to expression in vitro. of any within this region in a in IId/x promoter but to different or in a in IId/x promoter similar to that by of the whereas IId/x promoter activity by only However, of the of this region in a in IId/x promoter activity by these data whereas all of this element to be for IId/x promoter this we have a for effect on IId/x is of the sequence of this region no binding sites for identified muscle-specific transcription T. 1995; PubMed Scopus Google identified binding sites for members of the and complex factor family of transcription These factors are known to in 1999; PubMed Scopus Google Scholar), but have been directly in muscle-specific gene expression. is that as transcription factors are in this are studies to the binding to this for on this and and for in the and of the
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