Myogenic Regulatory Factors Can Activate TATA-containing Promoter Elements via an E-Box Independent Mechanism

Takeda, Shin‐ichi; North, Daniel L.; Diagana, Thierry T.; Miyagoe, Yuko; Lakich, M. M.; Whalen, Robert G.

doi:10.1074/jbc.270.26.15664

Cited by 43 publications

(44 citation statements)

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“…TATAIIB, the small PstI͞XbaI fragment of 40IIB-MyHC-CAT (ref. 24; kindly provided by Thierry Diagana, Institut Pasteur, Paris) was inserted into SVP-Luci. The NRSE oligonucleotide was then inserted into the NotI͞PstI sites to obtain NRSE-TATAIIB.…”

Section: Methodsmentioning

confidence: 99%

The neuron-restrictive silencer element: A dual enhancer/silencer crucial for patterned expression of a nicotinic receptor gene in the brain

Bessis

Champtiaux

Chatelin

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

121

116

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The neuron-restrictive silencer element (NRSE) has been identified in several neuronal genes and confers neuron specificity by silencing transcription in nonneuronal cells. NRSE is present in the promoter of the neuronal nicotinic acetylcholine receptor ␤2-subunit gene that determines its neuron-specific expression in the nervous system. Using transgenic mice, we show that NRSE may either silence or enhance transcription depending on the cellular context within the nervous system. In vitro in neuronal cells, NRSE activates transcription of synthetic promoters when located downstream in the 5 untranslated region, or at less than 50 bp upstream from the TATA box, but switches to a silencer when located further upstream. In contrast, in nonneuronal cells NRSE always functions as a silencer. Antisense RNA inhibition shows that the NRSE-binding protein REST contributes to the activation of transcription in neuronal cells.The mechanisms that account for transcriptional regulation in neurons are still poorly understood. Yet, increasing numbers of transcription factors (1-3) and DNA elements (4, 5) involved in neuron-specific transcription are now characterized. One of them, the neuron-restrictive silencer element (NRSE; ref. 6), also called RE (7), behaves as a regulatory sequence of several neuronal genes (8) by silencing transcription in nonneuronal cells (6,7,(9)(10)(11)(12)(13)(14). The silencing activity of NRSE was primarily studied by transient transfection assays in the promoter of the genes encoding type II sodium channel (NaII; 7) and SCG10 protein (6). It was also recognized in the genes encoding synapsin I (9), nicotinic acetylcholine receptor (nAChR) ␤2-subunit (5), Ng-CAM (11), m4 muscarinic receptor (12, 13), and choline acetyltransferase (ChAT; 14). On the basis of sequence homologies, Schoenherr et al. (8) recently identified about 20 genes carrying a NRSE-like sequence. Among these genes, 17 are expressed in the nervous system and in 10 of them, including the nAChR ␤2-subunit gene (5), NRSE is located in the 5Ј untranslated region (UTR) (ref. 15; see also refs. 16 and 17). Although important functional elements have already been found in the 5Ј UTR or in intragenic positions (4,(18)(19)(20), NRSE is, to our knowledge, the first element sharing a conserved intragenic position in several genes. The functional significance of such an unusual position remained to be explained.A transcription factor of the Gli-Krüppel zinc-finger family that binds to NRSE has recently been characterized in HeLa cells, and named neuron-restrictive silencer factor (NRSF; ref.15) or RE1 silencing transcription factor (REST; ref. 21, see also ref. 22). In vitro studies revealed that REST exhibits a transcriptional repressing activity on promoters that carry the NRSE sequence (15,21,23).In this work, we have analyzed the function of NRSE in the promoter of the mouse gene encoding the nAChR ␤2-subunit as well as the importance of its location within the promoter. In transgenic mice, we show that upon mutation of NRSE,...

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Section: Methodsmentioning

confidence: 99%

The neuron-restrictive silencer element: A dual enhancer/silencer crucial for patterned expression of a nicotinic receptor gene in the brain

Bessis

Champtiaux

Chatelin

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

121

116

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“…Both the distance between the E box and the TATA box and the distance from the mRNA start site have been shown to be important for transactivation of the desmin promoter by MyoD and myogenin (30). Therefore, it is possible that direct interactions between myogenin and the basal transcription machinery, potentially mediated by TATA-binding protein-associated factors (TAFs) specifically expressed in differentiated myotubes (31), depend on restricted spatial requirements that are crucial for caveolin-3 gene transcription.…”

Section: Fig 3 Promoter Sequence and Mrna Start Site Of The Human Cmentioning

confidence: 99%

The Basic Helix-Loop-Helix Transcription Factors Myogenin and Id2 Mediate Specific Induction of Caveolin-3 Gene Expression during Embryonic Development

Biederer¹,

Ries²,

Moser³

et al. 2000

Journal of Biological Chemistry

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Caveolin-3 protein is the only member of the caveolin family that shows a unique muscle-specific expression pattern, and loss of its functional activity causes muscular dystrophy. Caveolin-3 mRNA levels are dramatically increased during the formation of myotubes in the C2C12 cell line. In this study, we characterized the human caveolin-3 5-flanking region. Promoter analyses demonstrate that the proximal E box element serves as a myogenin binding site and is both necessary and sufficient to control caveolin-3 gene transcription. Transient transfection assays indicated that overexpression of myogenin activates caveolin-3 reporter gene expression, whereas Id2 overexpression inhibited caveolin-3 promoter activation by myogenin. A mutant Id2 protein lacking the HLH domain was not capable of suppressing myogenin-mediated activation. Determination of caveolin-3 transcript distribution patterns in vivo revealed that mRNA was first detectable at day 10 of gestation in the developing somites and heart. Caveolin-3 protein in myoblasts and myotubes was expressed in both the plasma membrane and vesicular structures. During skeletal myogenesis the level of Id2, an inhibitor of differentiation, decreases, allowing the induced basic helix-loop-helix transcription factor myogenin to form transcriptionally active heterodimers that bind to the caveolin-3 promoter and thereby mediate its transcription.

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“…Transcriptional Activity of the IIB MyHC Promoter Requires MEF-2 Binding to mAT1 and Oct-1 or MEF-2 Binding to mAT2-We have previously demonstrated that the presence of the mAT1 site or the mAT1 plus mAT2 sites leads to an increased level of transcriptional activation when included in reporter gene plasmid constructions used for transient transfection assays in quail myotubes (12) and C2 myotubes (10). (Note that in order for the IIB MyHC promoter to be active in C2 myogenic cells, co-transfection with an expression vector for one of the myogenic bHLH factors is necessary; this system has been analyzed and validated in our laboratory (10,39).)…”

Section: Figmentioning

confidence: 99%

“…(Note that in order for the IIB MyHC promoter to be active in C2 myogenic cells, co-transfection with an expression vector for one of the myogenic bHLH factors is necessary; this system has been analyzed and validated in our laboratory (10,39).) The 192-bp construct (Ϫ192 bp/ϩ13 bp of the IIB MyHC promoter immediately upstream of the CAT reporter gene), containing both mAT sites, is the most active of all the promoter constructs, even including those which are much larger (e.g.…”

Section: Figmentioning

confidence: 99%

MEF-2 and Oct-1 Bind to Two Homologous Promoter Sequence Elements and Participate in the Expression of a Skeletal Muscle-specific Gene

Lakich

Diagana²,

North³

et al. 1998

Journal of Biological Chemistry

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The murine adult IIB myosin heavy chain (IIB MyHC) gene is expressed only in certain skeletal muscle fibers. Within the proximal promoter are two A ؉ T-rich motifs, mAT1 and mAT2, which greatly enhance muscle-specific transcription; myogenic cells contain proteins that bind to these sequences. MEF-2 binds to both mAT1 and mAT2; a mutation abolishing its binding to mAT1 greatly diminishes the activity of the promoter. Both mAT motifs also form complexes with a protein requiring a target sequence typical of POU domain proteins, which migrate in electrophoretic mobility shift assays to the same position as a complex containing purified Oct-1 and which are supershifted by an antibody specific to Oct-1; this protein is therefore probably Oct-1. Footprinting experiments demonstrate that mAT1 is preferentially occupied by MEF-2 and mAT2 by Oct-1 and that these two proteins appear to bind cooperatively to their respective sites. Although the two mAT motifs have sequences that are very similar, they nonetheless exhibit distinct behaviors and perform differently in the activation of the promoter. The contribution of the IIB MyHC gene to specification of the myogenic phenotype is thus at least in part regulated by MEF-2 and Oct-1.

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Myogenic Regulatory Factors Can Activate TATA-containing Promoter Elements via an E-Box Independent Mechanism

Cited by 43 publications

References 50 publications

The neuron-restrictive silencer element: A dual enhancer/silencer crucial for patterned expression of a nicotinic receptor gene in the brain

The neuron-restrictive silencer element: A dual enhancer/silencer crucial for patterned expression of a nicotinic receptor gene in the brain

The Basic Helix-Loop-Helix Transcription Factors Myogenin and Id2 Mediate Specific Induction of Caveolin-3 Gene Expression during Embryonic Development

MEF-2 and Oct-1 Bind to Two Homologous Promoter Sequence Elements and Participate in the Expression of a Skeletal Muscle-specific Gene

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