Transgenic Analyses Reveal Developmentally Regulated Neuron- and Muscle-specific Elements in the Murine Neurofilament Light Chain Gene Promoter

We report here the developmental activity of regulatory elements that reside within 1.7 kilobases of the murine neurofilament light chain (NF-L) gene promoter. NF-L promoter activity is first detected at embryonic day 8.5 in neuroepithelial cells. Neuron-specific gene expression is maintained in the spinal cord until embryonic day 12.5 and at later developmental stages in the brain and sensory neuroepithelia. After day 14.5, the promoter becomes active in myogenic cells. Transgene expression in both neurons and muscle is consistent with the detection of endogenous NF-L transcript in both neuronal and myogenic tissues of neonates by reverse transcriptase-polymerase chain reaction. Neuron- and muscle-specific activities of the NF-L promoter decrease and are nearly undetectable after birth. Thus, the 1.7-kilobase NF-L promoter contains regulatory elements for initiation but not maintenance of transcription from the NF-L locus. Deletion analyses reveal that independent regulatory elements control the observed tissue-specific activities and implicate a potential MyoD binding site as the muscle-specific enhancer. Our results demonstrate that the NF-L promoter contains distinct regulatory elements for both neuron- and muscle-specific gene expression and that these activities are temporally separated during embryogenesis. We report here the developmental activity of regulatory elements that reside within 1.7 kilobases of the murine neurofilament light chain (NF-L) gene promoter. NF-L promoter activity is first detected at embryonic day 8.5 in neuroepithelial cells. Neuron-specific gene expression is maintained in the spinal cord until embryonic day 12.5 and at later developmental stages in the brain and sensory neuroepithelia. After day 14.5, the promoter becomes active in myogenic cells. Transgene expression in both neurons and muscle is consistent with the detection of endogenous NF-L transcript in both neuronal and myogenic tissues of neonates by reverse transcriptase-polymerase chain reaction. Neuron- and muscle-specific activities of the NF-L promoter decrease and are nearly undetectable after birth. Thus, the 1.7-kilobase NF-L promoter contains regulatory elements for initiation but not maintenance of transcription from the NF-L locus. Deletion analyses reveal that independent regulatory elements control the observed tissue-specific activities and implicate a potential MyoD binding site as the muscle-specific enhancer. Our results demonstrate that the NF-L promoter contains distinct regulatory elements for both neuron- and muscle-specific gene expression and that these activities are temporally separated during embryogenesis. Neurofilaments (NFs) 1The abbreviations used are: NF, neurofilament; NF-L, -M, -H, neurofilament light, medium, and heavy chain, respectively; RT-PCR, reverse transcriptase-polymerase chain reaction; dpc, days post-coitum; bp, base pair(s); kb, kilobase(s); PBS, phosphate-buffered saline; X-gal, 5-bromo-4-chloro-3-indolyl β-d-galactopyranoside; IE, immediate early; bHLH, basic-helix-loop-helix; CAT, chloramphenicol acetyltransferase.are a class of intermediate filaments that comprise the major cytoskeletal component of differentiated neurons. The mature filaments are assembled from three polypeptide subunits: light (NF-L), medium (NF-M) and heavy (NF-H) (for review, see Ref. 1Lee M.K. Cleveland D.W. Annu. Rev. Neurosci. 1996; 19: 187-217Crossref PubMed Scopus (385) Google Scholar). Each subunit is encoded by a distinct gene and is regulated differently during development, with NF-L and NF-M being expressed early at the time of neuronal cell differentiation and NF-H expressed much later (2Cochard P. Paulin D. J. Neurosci. 1984; 8: 2080-2094Crossref Google Scholar,3Julien J.-P. Meyer D. Flavell D. Hurst J. Grosveld F. Mol. Brain Res. 1986; 1: 243-250Crossref Scopus (157) Google Scholar). The levels of NF gene expression are low during embryonic development with an up-regulation of transcriptional activity at postnatal time points (4Carden M.J. Trojanowski J. Schlaepfer W. Lee V. J. Neurosci. 1987; 7: 3489-3504Crossref PubMed Google Scholar, 5Schlaepfer W. Bruce J. J. Neurosci. Res. 1990; 25: 39-49Crossref PubMed Scopus (78) Google Scholar, 6Schwartz M.L. Katagi C. Bruce J. Schlaepfer W. J. Biol. Chem. 1994; 269: 13444-13450Abstract Full Text PDF PubMed Google Scholar). The neuronal selectivity of neurofilaments has resulted in numerous studies aimed at identifying molecular mechanisms that regulate NF gene expression in neurons; nevertheless, little is understood about these processes. One approach to elucidate the regulation of gene expression is to fuse the genetic elements of interest to a reporter gene and monitor its expression in transfected cells or transgenic mice. In this way, the 5′-promoter regions of both the mouse and human NF genes have been shown to contain multiple positive and negative regulatory sites (7Shneidman P.S. Bruce J. Schwartz M.L. Schlaepfer W. Mol. Brain Res. 1992; 13: 127-138Crossref PubMed Scopus (28) Google Scholar, 8Ivanov T.R. Brown I.R. J. Neurosci. Res. 1992; 32: 149-158Crossref PubMed Scopus (16) Google Scholar, 9Yazdanbakhsh K. Fraser P. Kioussis D. Vidal M. Grosveld F. Lindenbaum M. Nucleic Acids Res. 1993; 21: 455-461Crossref PubMed Scopus (18) Google Scholar, 10Pospelov V.A. Pospelova T.V. Julien J.-P. Cell Growth Differ. 1994; 5: 187-196PubMed Google Scholar). However, in vivo attempts to identify neuron-specific elements within NF genes in transgenic mice have proven difficult (9Yazdanbakhsh K. Fraser P. Kioussis D. Vidal M. Grosveld F. Lindenbaum M. Nucleic Acids Res. 1993; 21: 455-461Crossref PubMed Scopus (18) Google Scholar, 11Beaudet L. Charron G. Houle D. Tretjakoff I. Peterson A. Julien J.-P. Gene ( Amst .). 1992; 116: 205-214Crossref PubMed Scopus (39) Google Scholar, 12Beaudet L. Cote F. Houle D. Julien J.-P. Mol. Brain Res. 1993; 18: 23-31Crossref PubMed Scopus (34) Google Scholar, 13Nakahira K. Ikenaka K. K. K. J. Biol. Chem. 1990; Full Text PDF PubMed Google Scholar, M. M. L. M. J. Res. 1993; Scopus Google Scholar, Mol. Brain Res. 1992; PubMed Scopus Google Scholar, L. A. C. Julien J.-P. M. J. Mol. Neurosci. 5: Scopus Google Scholar). report that of the human NF-L gene promoter are for neuronal expression (9Yazdanbakhsh K. Fraser P. Kioussis D. Vidal M. Grosveld F. Lindenbaum M. Nucleic Acids Res. 1993; 21: 455-461Crossref PubMed Scopus (18) Google report this for L. Charron G. Houle D. Tretjakoff I. Peterson A. Julien J.-P. Gene ( Amst .). 1992; 116: 205-214Crossref PubMed Scopus (39) Google Scholar). have been as a of the NF-L gene promoter regions in with a for regulatory elements (9Yazdanbakhsh K. Fraser P. Kioussis D. Vidal M. Grosveld F. Lindenbaum M. Nucleic Acids Res. 1993; 21: 455-461Crossref PubMed Scopus (18) Google Scholar, 11Beaudet L. Charron G. Houle D. Tretjakoff I. Peterson A. Julien J.-P. Gene ( Amst .). 1992; 116: 205-214Crossref PubMed Scopus (39) Google Scholar, L. A. C. Julien J.-P. M. J. Mol. Neurosci. 5: Scopus Google Scholar, C. M.J. Mol. Brain Res. 32: PubMed Scopus Google Scholar, G. M. Julien J.-P. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus (34) Google Scholar). in the of NF gene expression from in studies that report expression of reporter or NF genes the control of NF transfected cells (7Shneidman P.S. Bruce J. Schwartz M.L. Schlaepfer W. Mol. Brain Res. 1992; 13: 127-138Crossref PubMed Scopus (28) Google Scholar, 13Nakahira K. Ikenaka K. K. K. J. Biol. Chem. 1990; Full Text PDF PubMed Google Scholar, K. K. C. K. K. J. Biol. Chem. 1990; Full Text PDF PubMed Google Scholar, J.-P. Grosveld F. K. Flavell D. D. W. 1987; PubMed Scopus Google Scholar, M.J. Cleveland D.W. J. Cell Biol. PubMed Scopus Google Scholar, Lee J. Neurosci. PubMed Google Scholar, D. Nucleic Acids Res. 1990; 18: PubMed Scopus Google Scholar). In the of elements in the mouse NF-L gene that the NF-L transcript that both transcriptional and mechanisms a in NF gene expression M.L. Bruce J. P.S. Schlaepfer J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The of these in vivo studies in mice and not the developmental regulation of NF gene expression during embryogenesis. We that the initiation of transcription during development a in neuron-specific gene a the promoter from the murine NF-L gene that has been used to the neuronal expression of in A. PubMed Scopus Google Scholar, M. A. 1990; PubMed Scopus Google Scholar, M.J. Cleveland D.W. J. Cell Biol. 1990; PubMed Scopus Google Scholar, G. PubMed Scopus Google Scholar). In this embryonic expression of a gene the control of the murine NF-L promoter a of gene regulation in transgenic mice A. PubMed Scopus Google Scholar, C. Res. 1996; 5: PubMed Scopus Google Scholar). of the reporter in this is the transcriptional We report here the developmental and of tissue-specific regulatory regions of the murine NF-L gene promoter. Our results demonstrate that of the mouse NF-L promoter contain temporally and distinct elements that regulate transcription in neuronal and myogenic tissues during embryonic mice the in F. the Scholar). The and transgenic mouse have been A. PubMed Scopus Google Scholar, C. Res. 1996; 5: PubMed Scopus Google and The from G. by the the and site the site of A. PubMed Scopus Google Scholar). The by a the a in a and and C. to a of for mice M. L. G. C. F. A. PubMed Scopus Google used for and mice used as from transgenic mice from A. K. A. Nucleic Acids Res. 19: PubMed Scopus Google Scholar). The chain used to identify transgenic mice by of the of the the and for at at at from to to and to the of the J. Scholar). with a to the detected the at developmental stages after The of the of a as days The from the and in phosphate-buffered The separated from and used as a of embryonic for in in for at and 12.5 for and for The with three of at in a in the with and 5-bromo-4-chloro-3-indolyl The for at and by the of in the of from the as an control for the and is independent of C. Res. 1996; 5: PubMed Scopus Google Scholar). The by with and in in in of and in with a a by the in and at and with a from mice days after birth. spinal and tissues and in The in the of and to the by of with in the of with of the and or and of reverse for at at The for a of to to for used to and negative control for reaction. The used and and and and and separated by and by independent The of the murine NF-L promoter the as a contains 1.7 of the mouse NF-L promoter an to from both analyses the of the of and Gene The by within the NF-L promoter by with of the base and The of interest from and used to transgenic as at and for activity as the developmental activity of the murine neurofilament light chain gene have a of gene expression in transgenic mice A. PubMed Scopus Google C. Res. 1996; 5: PubMed Scopus Google Scholar). of independent transgenic One transgenic the the gene for the transcriptional from the control of the murine NF-L promoter. The transgenic the the reporter to the immediate early gene promoter. The promoter contains the elements for but is not in the of A. PubMed Scopus Google Scholar, C. Res. 1996; 5: PubMed Scopus Google Scholar). that both expression in cells the NF-L promoter is The of the used in these studies is in an mouse with the activity in of the brain and spinal cord of transgenic A. PubMed Scopus Google Scholar). We and mouse with the to the expression of an The activity of by a to a at dpc, and by from independent the of expression of the independent that expression the activity of the NF-L promoter not of these activity to the cells of the brain and spinal results demonstrate that expression of the in the an In reveal that the NF-L promoter is active in and reporter gene expression in the elucidate the and of NF-L promoter activity in the from and at stages of both and from The NF-L promoter first active at 8.5 activity to neuroepithelial cells promoter activity detected in at or to the In the observed in the of the the and in the activity detected in as as the and of the The of the spinal cord activity its and at with activity in the and the and as the and the The to as the early of cells. The to to the at the of the in regions little in the at in activity observed in the and The and the In the spinal the of cells and and to cells of the in the However, by 12.5 dpc, activity within the The of the and to and cells of the and of the positive the spinal cord at the in neuroepithelial cells in in cells in the activity observed with at three results demonstrate that the NF-L promoter expression to neuroepithelial activity within cells of the spinal at a of from are the of at and 12.5 activity is detected within development is a decrease in within the 12.5 dpc, activity is to a neuroepithelial cells in the spinal cord with in within the with a of cells by 12.5 We the developmental activity of the NF-L promoter by activity in at later dpc, neuron-specific activity in sensory neurons and cells of the and in a from an and and the positive an in tissues positive expression with The cells of the in the activity as the cells of the is to that cells in the in a with of and The of at later developmental time points a in neuron-specific activity from the NF-L promoter dpc, neuron-specific to the and The spinal cord in the as the The spinal cord and in regions negative dpc, within the brain to the and the and and these reveal that the NF-L promoter is neuron-specific during early The decrease in neuronal gene expression that the NF-L promoter contains regulatory elements for initiation of transcription early in development, elements to NF-L gene expression in neurons at later at later developmental observed in cells. dpc, the of the and as as muscle Thus, from the active in myogenic cells in to One day at dpc, for observed in the and and The of from these the of the cells as myogenic cells within the muscle is in both neuronal and and myogenic cells In cells of the activity a independent the to that observed with the activity within the of the the of the and the from the at and activity in or in brain or muscle activity detected in tissues and from mice at postnatal day and at and these reveal the of regulatory elements within the NF-L promoter that gene expression to myogenic cells at later developmental time However, to the activity observed in NF-L promoter activity in muscle not developmental stages or Thus, the NF-L promoter contains temporally regulated elements that but not expression in cell at developmental The of activity in or in tissues from mice an report that the an in the of mice A. PubMed Scopus Google Scholar). this reverse to the expression of the and the in neonates at day with the both the and or the and and control the or the the expression detected in that a or detected in spinal and muscle in the with the of in the for detected expression in mice a of both the and an detected in that the that the promoter is in the of in the of transgenic In spinal cord transcript detected in of and transcript detected in postnatal muscle or expression detected at the in the from both transgenic that the of expression to In these results the of transgenic mouse in that of the gene in that both a and In expression with in tissues the NF-L promoter is The activity in tissues the decrease in transcriptional activity of the NF-L promoter. the transcriptional activity of the transgenic NF-L promoter to that of the endogenous the expression of the endogenous NF-L gene in multiple tissues from mice by that a the first of gene expression from the endogenous NF-L in the brain and spinal cord In detected NF-L expression in muscle for or The detection of NF-L transcript in muscle with that observed for expression from The detection of endogenous NF-L in muscle of NF-L promoter as by activity and by in myogenic cells in transgenic and these results that the endogenous NF-L gene is active in muscle In demonstrate that the transcriptional activity of the gene is consistent with the activity of the transgenic NF-L promoter. identify regulatory elements that control NF-L gene the of the NF-L promoter. We of the of to is to and the K. Ikenaka K. K. K. J. Biol. Chem. 1990; Full Text PDF PubMed Google Scholar). base a of the mouse NF-L promoter to the NF-L from both the M. J. K. V. M. J. Neurosci. Res. PubMed Scopus Google and human V.A. Pospelova T.V. Julien J.-P. Cell Growth Differ. 1994; 5: 187-196PubMed Google Scholar). The promoter contains elements of at and both of are in the and mouse of at and both of are in the and mouse an of at is in both In a of is at regulatory sites reside within the promoter. The of these potential regulatory sites the and human NF-L is in to the transcription initiation site and the at base K. Ikenaka K. K. K. J. Biol. Chem. 1990; Full Text PDF PubMed Google contain potential binding sites for transcription as and Meyer Nucleic Acids Res. 1992; PubMed Scopus Google In the of the are a of binding sites for tissue-specific and regulated transcription with sites for and to regulatory in neuron-specific genes an binding been in gene expression J. Mol. Cell Biol. PubMed Google sites J. M. A. PubMed Scopus Google and a site Meyer Nucleic Acids Res. 1992; PubMed Scopus Google Scholar). potential binding sites for the expressed transcription J. Biol. Chem. 1994; 269: Full Text PDF PubMed Google are within the promoter interest is the of binding sites for myogenic and transcription sites at and C. 1992; PubMed Scopus Google are in the and mouse NF-L in the and mouse are an site at M. K. Mol. Biol. 8: PubMed Scopus Google an site at Mol. Biol. 1990; PubMed Scopus Google an at Meyer Nucleic Acids Res. 1992; PubMed Scopus Google and a potential binding site L. D. Mol. Biol. PubMed Scopus Google the of the NF-L promoter at with of to the The of these sites within the three that a in the expression of the NF-L The of myogenic transcription binding sites the expression of the in and myogenic and identify genetic regulatory elements that to the observed muscle-specific expression at dpc, a of in the NF-L promoter The first the promoter at base the binding site at and an at this to expression in both neuronal and myogenic tissues with activity in the brain and spinal cord as as in and to base potential and binding sites as as the at and the MyoD binding site at of gene in both neurons and However, to base a MyoD binding site at and to expression in muscle neuronal observed in the the of the spinal cord and of these observed in muscle that a muscle-specific and of the NF-L promoter and that the MyoD binding site at the muscle-specific promoter site is in both the and human NF-L In the decrease in neuronal that this of the promoter and contains elements for its of activity or in neurons. is to that within this the and comprise a that is to the NF-L promoter M. J. K. V. M. J. Neurosci. Res. PubMed Scopus Google and to the that of the human V.A. Pospelova T.V. Julien J.-P. Cell Growth Differ. 1994; 5: 187-196PubMed Google Scholar). the not contain transcription binding its of is of a regulatory to base myogenic transcription binding resulted in neuronal activity to the and analyses identify distinct the and promoter the promoter to gene expression in neuronal to the of neuronal activity with the promoter or with promoter elements and The of the and contains regulatory elements for both the and of neuronal The muscle-specific activity of the promoter promoter used and muscle-specific regulatory elements reside in the promoter and or with identify tissue-specific regulatory elements in the promoter of the mouse NF-L promoter. this that the regulatory muscle-specific activity is from the elements for neuronal this have the activity of the murine NF-L promoter during embryonic development a transgenic mouse the transcriptional The gene is expressed the control of the murine NF-L promoter and is used to a reporter the is to the promoter A. PubMed Scopus Google Scholar, C. Res. 1996; 5: PubMed Scopus Google Scholar). We transgenic mouse to the embryonic expression of the mouse NF-L promoter by of activity from of an that both a and expression within the with independent mouse in to the The developmental activity of the promoter by for gene expression at developmental time activity to for cells of the and detected at 8.5 in neuroepithelial cells. The first of NF-L has been detected by in the and at in the spinal cord (2Cochard P. Paulin D. J. Neurosci. 1984; 8: 2080-2094Crossref Google Scholar). The detection of expression NF-L is consistent with the of promoter activity to or with the cell of neuronal as the not for at later developmental that the NF-L promoter not its activity in mature neurons. dpc, neuronal NF-L promoter activity to the and with activity in the and these that the NF-L promoter transcription in a neuron-specific at early stages of neuronal studies the human NF-L promoter report that a or of the promoter neuron-specific gene expression in transgenic at L. A. C. Julien J.-P. M. J. Mol. Neurosci. 5: Scopus Google Scholar, G. M. Julien J.-P. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus (34) Google Scholar). However, in transgenic that the promoter used and by the transgenic of neuronal The to identify a neuron-specific in the promoter regions of the NF genes has to the that regions of the NF-L gene are for expression in transgenic mice L. Charron G. Houle D. Tretjakoff I. Peterson A. Julien J.-P. Gene ( Amst .). 1992; 116: 205-214Crossref PubMed Scopus (39) Google Scholar, L. A. C. Julien J.-P. M. J. Mol. Neurosci. 5: Scopus Google Scholar, G. M. Julien J.-P. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus (34) Google Scholar). Our results in transgenic the of neuron-specific regulatory elements in the of the mouse NF-L a consistent of NF-L promoter activity in transgenic mice. independent transgenic that the a of Thus, that the promoter reporter gene expression to the in a for the to results in the time for the to transgenic that the the murine NF-L to that from human and contain regulatory elements that gene 1.7 of promoter studies used much or promoter The or of regulatory elements the expression from the promoter. a transcriptional to the reporter gene in a transgenic mouse with transcription A. PubMed Scopus Google Scholar, P. A. J. 7: PubMed Scopus Google Scholar, A. 1984; PubMed Scopus Google Scholar, J. 1990; PubMed Scopus Google Scholar, Full Text PDF PubMed Scopus Google Scholar, K. Peterson W. Biol. 1993; PubMed Scopus Google and is that reporter gene The from results is that the of the mouse NF-L promoter is active in the during early The developmental activity of the NF-L promoter time the shown to of an in the brain of mice A. PubMed Scopus Google Scholar). However, an activity not detected in at developmental stages later or at three postnatal time the in postnatal spinal and muscle detected in the brain with for the spinal cord of transgenic results that the NF-L promoter is at this time or that a cells the in the expression low to detected the In with the from embryonic results that the NF-L promoter contains elements for but not gene expression within neurons. NF-L promoter activity detected in muscle as by of and results demonstrate that the NF-L promoter is active in cell in in muscle cells. the promoter active in these the expression of NF-L not detected by in tissues at 14.5, and in the mouse (2Cochard P. Paulin D. J. Neurosci. 1984; 8: 2080-2094Crossref Google is consistent with from cell that detected NF but not of NF genes cell (7Shneidman P.S. Bruce J. Schwartz M.L. Schlaepfer W. Mol. Brain Res. 1992; 13: 127-138Crossref PubMed Scopus (28) Google Scholar, 13Nakahira K. Ikenaka K. K. K. J. Biol. Chem. 1990; Full Text PDF PubMed Google Scholar, K. K. C. K. K. J. Biol. Chem. 1990; Full Text PDF PubMed Google Scholar, J.-P. Grosveld F. K. Flavell D. D. W. 1987; PubMed Scopus Google Scholar, M.J. Cleveland D.W. J. Cell Biol. PubMed Scopus Google Scholar, Lee J. Neurosci. PubMed Google Scholar). Our that mechanisms regulate the tissue-specific expression of NF reveal that muscle-specific regulatory elements to within the NF expression from has been vivo in transgenic mice. promoter from the NF-L gene expression of a reporter gene in and muscle M. M. L. M. J. Res. 1993; Scopus Google and neurofilaments have been observed in muscle by M.J. Cleveland D.W. J. Cell Biol. 1990; PubMed Scopus Google Scholar, Cleveland D.W. 1993; Full Text PDF PubMed Scopus Google Scholar). is to in NF-M has been from of We that elements NF expression in muscle reside within the NF-L promoter. The transcriptional activity of the endogenous NF-L gene by and detected in spinal and muscle from that in the endogenous NF-L is active in in muscle NF-L not detected in results are consistent with that the NF-L promoter is active in muscle cells during embryogenesis. The of activity in myogenic cells at but not later stages of development as in the NF-L promoter is of but not tissue-specific gene that molecular for NF gene expression within the NF-L promoter and that mechanisms the expression of NF to neurons. identify potential regulatory elements in NF-L gene of from the murine NF-L promoter. The the mouse and NF-L and with the human NF-L promoter with to transcription binding sites to the promoter from to and the to the transcription from to in the promoter is the of binding sites J. M. A. PubMed Scopus Google site V.A. Pospelova T.V. Julien J.-P. Cell Growth Differ. 1994; 5: 187-196PubMed Google Scholar, 13Nakahira K. Ikenaka K. K. K. J. Biol. Chem. 1990; Full Text PDF PubMed Google Scholar, Meyer Nucleic Acids Res. 1992; PubMed Scopus Google and three potential sites Meyer Nucleic Acids Res. 1992; PubMed Scopus Google Scholar). have been shown to in to the promoter of the neuron-specific human gene D. G. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). expression has been detected in the brain and in mice A. P. 1992; PubMed Scopus Google and in of spinal neurons in the and Thus, is that these sites are in expression in the However, promoter studies that the promoter to expression in neuronal and that promoter regions are for the neuronal activity of the NF-L promoter. The promoter analyses that the promoter contains elements for both the neuron- muscle-specific activity of the promoter. binding sites for myogenic of the class are in the sites for MyoD binding C. 1992; PubMed Scopus Google site for M. K. Mol. Biol. 8: PubMed Scopus Google site for Mol. Biol. 1990; PubMed Scopus Google and an Meyer Nucleic Acids Res. 1992; PubMed Scopus Google Scholar). Deletion of the promoter from to base or resulted in neuronal the MyoD binding site at as the muscle-specific enhancer. The neuronal and to neuronal demonstrate that the promoter and contains distinct and independent elements for and neuron-specific gene that the of activity in neurons the of elements in the to of the promoter with is to that the of expression in muscle in transgenic not with the of expression of myogenic genes M. 1992; 8: Full Text PDF PubMed Scopus Google Scholar). gene is both and temporally regulated in its expression during muscle development 1994; PubMed Google Scholar, G. Mol. Biol. 1996; PubMed Scopus Google as development gene expression is to the brain J. J. Neurosci. PubMed Google Scholar). from muscle to has been as an of for transcriptional mechanisms in neuron- and muscle-specific gene The NF-L promoter of a regulatory in muscle and neurons with a temporally regulated in However, in this expression from neurons to muscle cells. these the that temporally are in these that control gene expression in distinct tissues during embryonic In that a 1.7 of the murine NF-L promoter gene expression during in transgenic mice. of the developmental activity of this promoter and regulation that a to muscle-specific gene expression during later developmental Deletion analyses that distinct elements within the promoter regulate the neuron- and muscle-specific promoter The of promoter activity in both neuronal and muscle cells that initiation of transcription from the NF-L promoter is to cell or differentiation and that regulatory elements to NF-L transcription in differentiated cells. We are to for M. for of and for in the transgenic mouse and in the of We J. for