Biomaterial Database

FMR1 enhancer is regulated by cAMP through a cAMP-responsive element. 1997

W L Hwu, and T R Wang, and Y M Lee

Department of Medical Genetics and Pediatrics, National Taiwan University Hospital, Taipei, R.O.C.

FMR1 (Fra X Mental Retardation 1), a gene of unknown function, is responsible for an important hereditary mental retardation, the fragile X syndrome. In this study, a 22-bp enhancer (methylation sensitive element, MSE) in the FMR1 promoter was defined by DNase I footprinting assay, and the binding of this element by nuclear factor was prevented by DNA CpG methylation. A cAMP-responsive element (CRE)-like sequence and a myc-binding sequence in MSE were identified. In the transfection assay, MSE demonstrated a strong, methylation-sensitive enhancer activity. MSE could be bound by recombinant CRE-binding protein (CREB), and its activity was stimulated by CREB in a co-transfection assay. In PC12 cells, forskolin elevated MSE activity several fold, and this induction was abolished in CRE mutants. The involvement of cAMP in the expression of FMR1 should be a clue to both the function of FMR1 and the pathogenesis of fragile X syndrome.

UI	MeSH Term	Description	Entries
D009419	Nerve Tissue Proteins		Proteins, Nerve Tissue,Tissue Proteins, Nerve
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D012045	Regulatory Sequences, Nucleic Acid	Nucleic acid sequences involved in regulating the expression of genes.	Nucleic Acid Regulatory Sequences,Regulatory Regions, Nucleic Acid (Genetics),Region, Regulatory,Regions, Regulatory,Regulator Regions, Nucleic Acid,Regulatory Region,Regulatory Regions
D004742	Enhancer Elements, Genetic	Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.	Enhancer Elements,Enhancer Sequences,Element, Enhancer,Element, Genetic Enhancer,Elements, Enhancer,Elements, Genetic Enhancer,Enhancer Element,Enhancer Element, Genetic,Enhancer Sequence,Genetic Enhancer Element,Genetic Enhancer Elements,Sequence, Enhancer,Sequences, Enhancer
D005576	Colforsin	Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.	Coleonol,Forskolin,N,N-Dimethyl-beta-alanine-5-(acetyloxy)-3-ethenyldodecahydro-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho(2,1-b)pyran-6-yl Ester HCl,NKH 477,NKH-477,NKH477
D005600	Fragile X Syndrome	A condition characterized genotypically by mutation of the distal end of the long arm of the X chromosome (at gene loci FRAXA or FRAXE) and phenotypically by cognitive impairment, hyperactivity, SEIZURES, language delay, and enlargement of the ears, head, and testes. INTELLECTUAL DISABILITY occurs in nearly all males and roughly 50% of females with the full mutation of FRAXA. (From Menkes, Textbook of Child Neurology, 5th ed, p226)	FRAXA Syndrome,FRAXE Syndrome,Martin-Bell Syndrome,Fra(X) Syndrome,Fragile X Mental Retardation Syndrome,Fragile X-F Mental Retardation Syndrome,Mar (X) Syndrome,Marker X Syndrome,Mental Retardation, X-Linked, Associated With Fragile Site Fraxe,Mental Retardation, X-Linked, Associated With Marxq28,X-Linked Mental Retardation and Macroorchidism,FRAXA Syndromes,FRAXE Syndromes,Fragile X Syndromes,Marker X Syndromes,Martin Bell Syndrome,Syndrome, FRAXA,Syndrome, FRAXE,Syndrome, Fragile X,Syndrome, Marker X,Syndrome, Martin-Bell,Syndromes, FRAXA,Syndromes, FRAXE,Syndromes, Fragile X,Syndromes, Marker X,X Linked Mental Retardation and Macroorchidism
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000242	Cyclic AMP	An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.	Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D016271	Proto-Oncogene Proteins c-myc	Basic helix-loop-helix transcription factors encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.	L-myc Proteins,N-myc Proteins,c-myc Proteins,myc Proto-Oncogene Proteins,p62(c-myc),Proto-Oncogene Products c-myc,Proto-Oncogene Proteins myc,myc Proto-Oncogene Product p62,p62 c-myc,L myc Proteins,N myc Proteins,Proteins myc, Proto-Oncogene,Proto Oncogene Products c myc,Proto Oncogene Proteins c myc,Proto Oncogene Proteins myc,Proto-Oncogene Proteins, myc,c myc Proteins,myc Proto Oncogene Product p62,myc Proto Oncogene Proteins,myc, Proto-Oncogene Proteins,p62 c myc
D016601	RNA-Binding Proteins	Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.	Double-Stranded RNA-Binding Protein,Double-Stranded RNA-Binding Proteins,ds RNA-Binding Protein,RNA-Binding Protein,ds RNA-Binding Proteins,Double Stranded RNA Binding Protein,Double Stranded RNA Binding Proteins,Protein, Double-Stranded RNA-Binding,Protein, ds RNA-Binding,RNA Binding Protein,RNA Binding Proteins,RNA-Binding Protein, Double-Stranded,RNA-Binding Protein, ds,RNA-Binding Proteins, Double-Stranded,ds RNA Binding Protein