Early Growth Response Protein 1
Early Growth Response Transcription Factors
Early Growth Response Protein 3
Early Growth Response Protein 2
Immediate-Early Proteins
Transcription Factors
DNA-Binding Proteins
Promoter Regions, Genetic
Gene Expression Regulation
RNA, Messenger
DNA Methylation
Encyclopedias as Topic
CpG Islands
Methylation
DNA (Cytosine-5-)-Methyltransferase
Epigenesis, Genetic
Thyroid hormone effects on Krox-24 transcription in the post-natal mouse brain are developmentally regulated but are not correlated with mitosis. (1/1242)
Krox-24 (NGFI-A, Egr-1) is an immediate-early gene encoding a zinc finger transcription factor. As Krox-24 is expressed in brain areas showing post-natal neurogenesis during a thyroid hormone (T3)-sensitive period, we followed T3 effects on Krox-24 expression in newborn mice. We analysed whether regulation was associated with changes in mitotic activity in the subventricular zone and the cerebellum. In vivo T3-dependent Krox-24 transcription was studied by polyethylenimine-based gene transfer. T3 increased transcription from the Krox-24 promoter in both areas studied at post-natal day 2, but was without effect at day 6. An intact thyroid hormone response element (TRE) in the Krox-24 promoter was necessary for these inductions. These stage-dependent effects were also seen in endogenous Krox-24 mRNA levels: activation at day 2 and no effect at day 6. Moreover, similar results were obtained by examining beta-galactosidase expression in heterozygous mice in which one allele of the Krox-24 gene was disrupted with an inframe Lac-Z insertion. However, bromodeoxyuridine incorporation showed mitosis to continue through to day 6. We conclude first, that T3 activates Krox-24 transcription during early post-natal mitosis but that this effect is extinguished as development proceeds and second, loss of T3-dependent Krox-24 expression is not correlated with loss of mitotic activity. (+info)Nerve growth factor induces zif268 gene expression via MAPK-dependent and -independent pathways in PC12D cells. (2/1242)
In this study we examined the contribution of MAPK1 and 2 [also known as extracellular signal-regulated kinases (ERK)-1 and 2] to the induction of zif268 mRNA in PC12D cells by using two methods to block the activation of these kinases. In one set of experiments, we inhibited the activation of MAPK by pretreating cells with PD098059, a specific inhibitor of MEK (MAPKK), the immediate upstream activator of MAPK. In the second set of experiments, we blocked the activation of MAPK by overexpressing N17Ras, a dominant-negative form of Ha-Ras. These two approaches yielded similar results and showed that inhibition of MAPK blocks less than half of the induction of zif268 mRNA by NGF. Much of the residual induction of zif268 mRNA is blocked by low concentrations of wortmannin, an inhibitor of phosphatidylinositol (PI) 3-kinase. Since PI 3-kinase was previously shown to function upstream in epidermal growth factor (EGF)-mediated activation of c-Jun N-terminal kinase (JNK), and JNK is known to phosphorylate and activate transcription factors that regulate the expression of zif268, we investigated the role of JNK in the induction of zif268 mRNA by NGF. Stimulation of PC12D cells with NGF weakly activates JNK, but this activation is enhanced rather than inhibited by pretreatment with wortmannin, suggesting that JNK does not function downstream of PI 3-kinase in the induction of zif268 mRNA. A role for JNK in the induction of the zif268 gene is indicated, however, by the fact that cotransfection of expression vectors encoding JIP-1 or the JNK binding domain of JIP-1, which act as dominant-negative inhibitors of JNK, partially blocks the NGF-mediated induction of a luciferase reporter gene linked to the zif268 promoter. Together, these results suggest that MAPK, PI-3 kinase and JNK each play a role in the induction of zif268 gene expression by NGF in PC12D cells. (+info)Serum response elements activate and cAMP responsive elements inhibit expression of transcription factor Egr-1 in synovial fibroblasts of rheumatoid arthritis patients. (3/1242)
Analyzing the induction kinetics and promoter elements regulating the expression of the transcription factor Egr-1, we found elevated levels of Egr-1-encoding mRNA in synovial fibroblasts of rheumatoid arthritis (RA) patients when compared to controls. By contrast, synovial lymphocytes and macrophages do not show an elevated Egr-1 transcription. Therefore, the overexpression of Egr-1 may serve as a diagnostic marker to characterize synovial fibroblasts of RA patients. To study the regulatory mechanisms controlling Egr-1 expression we analyzed the function of transcription factor binding sites located in the Egr-1 promoter. Individual transcription factor binding sites within the Egr-1 promoter were specifically mutated and Egr-1 promoter activity was tested using reporter gene constructs. Our experiments demonstrate that serum response elements are the main positive regulators and binding to a cAMP responsive element represents the major negative regulator for Egr-1 expression in synovial fibroblasts. In addition, we functionally defined a new element, which was not yet described in the human Egr-1 promoter and which serves as a second negative regulatory element for Egr-1 expression. Therefore increased serum response factor activity or failure of Egr-1 repressing signals may account for Egr-1 overexpression in RA synovial fibroblasts. (+info)TAFII250, Egr-1, and D-type cyclin expression in mice and neonatal rat cardiomyocytes treated with doxorubicin. (4/1242)
Differential display identified that gene fragment HA220 homologous to the transcriptional activator factor II 250 (TAFII250) gene, or CCG1, was increased in hypertrophied rodent heart. To determine whether TAFII250 gene expression is modified after cardiac damage, we measured TAFII250 expression in vivo in mouse hearts after injection of the cardiotoxic agent doxorubicin (DXR) and in vitro in DXR-treated isolated rat neonatal cardiomyocytes. In vivo atrial natriuretic factor (ANF), beta-myosin heavy chain (beta-MHC), Egr-1, and TAFII250 expression increased with dose and time after a single DXR injection, but only ANF and beta-MHC expression were increased after multiple injections. After DXR treatment of neonatal cardiomyocytes we found decreased ANF, alpha-MHC, Egr-1, and TAFII250 expression. Expression of the TAFII250-regulated genes, the D-type cyclins, was increased after a single injection in adult mice and was decreased in DXR-treated cardiomyocytes. Thus expression of Erg-1, TAFII250, and the D-type cyclins is modulated after cardiotoxic damage in adult and neonatal heart. (+info)Egr-1 is a downstream effector of GnRH and synergizes by direct interaction with Ptx1 and SF-1 to enhance luteinizing hormone beta gene transcription. (5/1242)
Pituitary gonadotropins are critical regulators of gonadal development and function. Expression and secretion of the mature hormones are regulated by gonadotropin-releasing hormone (GnRH), which is itself secreted from the hypothalamus. GnRH stimulation of gonadotropin expression and secretion occurs through the G-protein-linked phospholipase C/inositol triphosphate intracellular signaling pathway, which ultimately leads to protein kinase C (PKC) activation and increased intracellular calcium levels. Transcription factors mediating the effects of GnRH-induced signals on transcription of gonadotropin genes have not yet been identified. Recent studies have identified key factors involved in luteinizing hormone beta (LHbeta) gonadotropin gene transcription: the nuclear receptor SF-1, the bicoid-related homeoprotein Ptx1 (Pitx1), and the immediate-early Egr-1 gene. We now show that GnRH is a potent stimulator of Egr-1, but not Ptx1 or SF-1, expression. Further, Egr-1 activation of the LHbeta promoter is specifically enhanced by PKC, in agreement with a role for Egr-1 in mediating a GnRH effect on transcription. Egr-1 interacts directly with Ptx1 and with SF-1, leading to an enhancement of Ptx1- and SF-1-induced LHbeta transcription. Thus, Egr-1 is a likely transcriptional mediator of GnRH-induced signals for activation of the LHbeta gene. (+info)COUP-TF upregulates NGFI-A gene expression through an Sp1 binding site. (6/1242)
The formation of various tissues requires close communication between two groups of cells, epithelial and mesenchymal cells. COUP-TFs are transcription factors which have been shown to have functions in embryonic development. COUP-TFI is expressed mainly in the nervous system, and its targeted deletion leads to defects in the central and peripheral nervous systems. COUP-TFII is highly expressed in the mesenchymal component of the developing organs. A null mutation of COUP-TFII results in the malformation of the heart and blood vessels. From their expression pattern, we proposed that COUP-TFs regulate paracrine signals important for mesenchymal cell-epithelial cell interactions. In order to identify genes regulated by COUP-TF in this process, a rat urogenital mesenchymal cell line was stably transfected with a COUP-TFI expression vector. We found that NGFI-A, a gene with important functions in brain, organ, and vasculature development, has elevated mRNA and protein levels upon overexpression of COUP-TFI in these cells. A study of the promoter region of this gene identified a COUP-TF-responsive element between positions -64 and -46. Surprisingly, this region includes binding sites for members of the Sp1 family of transcription factors but no COUP-TF binding site. Mutations that abolish the Sp1 binding activity also impair the transactivation of the NGFI-A promoter by COUP-TF. Two regions of the COUP-TF molecule are shown to be important for NGFI-A activation: the DNA binding domain and the extreme C terminus of the putative ligand binding domain. The C-terminal region is likely to be important for interaction with coactivators. In fact, the coactivators p300 and steroid receptor activator 1 can enhance the transactivation of the NGFI-A promoter induced by COUP-TFI. Finally, we demonstrated that COUP-TF can directly interact with Sp1. Taken together, these results suggest that NGFI-A is a target gene for COUP-TFs and that the Sp1 family of transcription factors mediates its regulation by COUP-TFs. (+info)The ras oncogene inhibits growth factor inducibility of early response genes, and promotes selectively expression of NGFI-A in a PC12 cell line. (7/1242)
Expression of oncogenic Ras in UR61 cells (a PC12 subclone) results in neuronal differentiation. We have observed that the oncoprotein selectively increased the levels of NGFI-A transcripts, but was unable to induce NGFI-B or c-fos transcripts. In contrast, nerve growth factor (NGF) elicited a strong induction of the three immediate early genes (IEGs). Thus, activation of Ras alone is sufficient for the induction of NGFI-A by NGF, whereas an additional pathway(s), besides Ras, is required for the stimulation of NGFI-B and c-fos gene expression. These results show that the acquisition of a neuronal phenotype does not correlate with induction of IEG expression. Additionally, Ras markedly reduces the response of the three genes to NGF and to other growth factors. This attenuation could reflect a negative regulatory mechanism acting on signalling pathways normally stimulated by growth factor receptors. (+info)GTPase deficient mutant of G(alpha13) regulates the expression of Egr-1 through the small GTPase Rho. (8/1242)
The alpha-subunit of the heterotrimeric G protein G13 regulate cell growth, differentiation and apoptosis in different cell types. Expression of the constitutively activated mutant of G(alpha)13 (G(alpha13)QL) increases the expression of Egr-1, an immediate-early response gene that is identified to be involved in cell growth, differentiation, and apoptosis. Here we report that G(alpha13)QL activates the promoter of Egr-1 through specific sequence which includes the characteristic CArG boxes. We also demonstrate that the G(alpha13)QL activation of Egr-1 promoter is mediated by the Ras-like small GTPase Rho. (+info)Early Growth Response Protein 1 (EGR1) is a transcription factor that belongs to the EGR family of proteins, which are also known as zinc finger transcription factors. EGR1 plays crucial roles in various biological processes, including cell proliferation, differentiation, and apoptosis. It regulates gene expression by binding to specific DNA sequences in the promoter regions of target genes.
EGR1 is rapidly induced in response to a variety of stimuli, such as growth factors, neurotransmitters, and stress signals. Once induced, EGR1 modulates the transcription of downstream target genes involved in different signaling pathways, such as mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), and nuclear factor kappa B (NF-κB) pathways.
EGR1 has been implicated in several physiological and pathological processes, including development, learning and memory, neurodegeneration, and cancer. In the context of cancer, EGR1 can act as a tumor suppressor or an oncogene, depending on the cellular context and the specific target genes it regulates.
Early growth response (EGR) transcription factors are a family of proteins that play crucial roles in the regulation of gene expression in response to various cellular stimuli and stress. These transcription factors are involved in several biological processes, including cell proliferation, differentiation, survival, and apoptosis.
The EGR family consists of four members: EGR1 (also known as ZIF268, NGFI-A, or KROX24), EGR2 (KROX20), EGR3, and EGR4 (NR4A2). They share a highly conserved DNA-binding domain called the zinc finger domain, which allows them to bind to specific DNA sequences known as EGR response elements (EGR-REs) in the promoter regions of their target genes.
Upon activation by various signals such as growth factors, hormones, neurotransmitters, or stressors, EGR transcription factors undergo rapid phosphorylation and translocate to the nucleus, where they bind to EGR-REs and regulate the transcription of their target genes. The expression of EGR genes is tightly controlled and often serves as a critical step in signal transduction pathways that mediate various cellular responses. Dysregulation of EGR transcription factors has been implicated in several diseases, including cancer, neurodegenerative disorders, and cardiovascular diseases.
Early Growth Response Protein 3 (EGR3) is a transcription factor that belongs to the EGR family of proteins, which are involved in various biological processes such as cell proliferation, differentiation, and apoptosis. EGR3 is rapidly induced in response to a variety of stimuli including growth factors, neurotransmitters, and stress signals. It regulates gene expression by binding to specific DNA sequences and modulating the transcription of target genes. EGR3 has been implicated in several physiological and pathological processes, including neuronal development, learning and memory, immune function, and cancer.
Early Growth Response Protein 2 (EGR2) is a transcription factor that belongs to the EGR family of proteins, which are involved in various biological processes such as cell proliferation, differentiation, and apoptosis. EGR2 is specifically known to play crucial roles in the development and function of the nervous system, including the regulation of neuronal survival, axon guidance, and myelination. It is also expressed in immune cells and has been implicated in the regulation of immune responses. Mutations in the EGR2 gene have been associated with certain neurological disorders and diseases, such as Charcot-Marie-Tooth disease type 1B and congenital hypomyelinating neuropathy.
Immediate-early proteins (IEPs) are a class of regulatory proteins that play a crucial role in the early stages of gene expression in viral infection and cellular stress responses. These proteins are synthesized rapidly, without the need for new protein synthesis, after the induction of immediate-early genes (IEGs).
In the context of viral infection, IEPs are often the first proteins produced by the virus upon entry into the host cell. They function as transcription factors that bind to specific DNA sequences and regulate the expression of early and late viral genes required for replication and packaging of the viral genome.
IEPs can also be involved in modulating host cell signaling pathways, altering cell cycle progression, and inducing apoptosis (programmed cell death). Dysregulation of IEPs has been implicated in various diseases, including cancer and neurological disorders.
It is important to note that the term "immediate-early proteins" is primarily used in the context of viral infection, while in other contexts such as cellular stress responses or oncogene activation, these proteins may be referred to by different names, such as "early response genes" or "transcription factors."
Transcription factors are proteins that play a crucial role in regulating gene expression by controlling the transcription of DNA to messenger RNA (mRNA). They function by binding to specific DNA sequences, known as response elements, located in the promoter region or enhancer regions of target genes. This binding can either activate or repress the initiation of transcription, depending on the properties and interactions of the particular transcription factor. Transcription factors often act as part of a complex network of regulatory proteins that determine the precise spatiotemporal patterns of gene expression during development, differentiation, and homeostasis in an organism.
DNA-binding proteins are a type of protein that have the ability to bind to DNA (deoxyribonucleic acid), the genetic material of organisms. These proteins play crucial roles in various biological processes, such as regulation of gene expression, DNA replication, repair and recombination.
The binding of DNA-binding proteins to specific DNA sequences is mediated by non-covalent interactions, including electrostatic, hydrogen bonding, and van der Waals forces. The specificity of binding is determined by the recognition of particular nucleotide sequences or structural features of the DNA molecule.
DNA-binding proteins can be classified into several categories based on their structure and function, such as transcription factors, histones, and restriction enzymes. Transcription factors are a major class of DNA-binding proteins that regulate gene expression by binding to specific DNA sequences in the promoter region of genes and recruiting other proteins to modulate transcription. Histones are DNA-binding proteins that package DNA into nucleosomes, the basic unit of chromatin structure. Restriction enzymes are DNA-binding proteins that recognize and cleave specific DNA sequences, and are widely used in molecular biology research and biotechnology applications.
Promoter regions in genetics refer to specific DNA sequences located near the transcription start site of a gene. They serve as binding sites for RNA polymerase and various transcription factors that regulate the initiation of gene transcription. These regulatory elements help control the rate of transcription and, therefore, the level of gene expression. Promoter regions can be composed of different types of sequences, such as the TATA box and CAAT box, and their organization and composition can vary between different genes and species.
'Gene expression regulation' refers to the processes that control whether, when, and where a particular gene is expressed, meaning the production of a specific protein or functional RNA encoded by that gene. This complex mechanism can be influenced by various factors such as transcription factors, chromatin remodeling, DNA methylation, non-coding RNAs, and post-transcriptional modifications, among others. Proper regulation of gene expression is crucial for normal cellular function, development, and maintaining homeostasis in living organisms. Dysregulation of gene expression can lead to various diseases, including cancer and genetic disorders.
Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.
DNA methylation is a process by which methyl groups (-CH3) are added to the cytosine ring of DNA molecules, often at the 5' position of cytospine phosphate-deoxyguanosine (CpG) dinucleotides. This modification is catalyzed by DNA methyltransferase enzymes and results in the formation of 5-methylcytosine.
DNA methylation plays a crucial role in the regulation of gene expression, genomic imprinting, X chromosome inactivation, and suppression of transposable elements. Abnormal DNA methylation patterns have been associated with various diseases, including cancer, where tumor suppressor genes are often silenced by promoter methylation.
In summary, DNA methylation is a fundamental epigenetic modification that influences gene expression and genome stability, and its dysregulation has important implications for human health and disease.
An encyclopedia is a comprehensive reference work containing articles on various topics, usually arranged in alphabetical order. In the context of medicine, a medical encyclopedia is a collection of articles that provide information about a wide range of medical topics, including diseases and conditions, treatments, tests, procedures, and anatomy and physiology. Medical encyclopedias may be published in print or electronic formats and are often used as a starting point for researching medical topics. They can provide reliable and accurate information on medical subjects, making them useful resources for healthcare professionals, students, and patients alike. Some well-known examples of medical encyclopedias include the Merck Manual and the Stedman's Medical Dictionary.
CpG islands are defined as short stretches of DNA that are characterized by a higher than expected frequency of CpG dinucleotides. A dinucleotide is a pair of adjacent nucleotides, and in the case of CpG, C represents cytosine and G represents guanine. These islands are typically found in the promoter regions of genes, where they play important roles in regulating gene expression.
Under normal circumstances, the cytosine residue in a CpG dinucleotide is often methylated, meaning that a methyl group (-CH3) is added to the cytosine base. However, in CpG islands, methylation is usually avoided, and these regions tend to be unmethylated. This has important implications for gene expression because methylation of CpG dinucleotides in promoter regions can lead to the silencing of genes.
CpG islands are also often targets for transcription factors, which bind to specific DNA sequences and help regulate gene expression. The unmethylated state of CpG islands is thought to be important for maintaining the accessibility of these regions to transcription factors and other regulatory proteins.
Abnormal methylation patterns in CpG islands have been associated with various diseases, including cancer. In many cancers, CpG islands become aberrantly methylated, leading to the silencing of tumor suppressor genes and contributing to the development and progression of the disease.
Methylation, in the context of genetics and epigenetics, refers to the addition of a methyl group (CH3) to a molecule, usually to the nitrogenous base of DNA or to the side chain of amino acids in proteins. In DNA methylation, this process typically occurs at the 5-carbon position of cytosine residues that precede guanine residues (CpG sites) and is catalyzed by enzymes called DNA methyltransferases (DNMTs).
DNA methylation plays a crucial role in regulating gene expression, genomic imprinting, X-chromosome inactivation, and suppression of repetitive elements. Hypermethylation or hypomethylation of specific genes can lead to altered gene expression patterns, which have been associated with various human diseases, including cancer.
In summary, methylation is a fundamental epigenetic modification that influences genomic stability, gene regulation, and cellular function by introducing methyl groups to DNA or proteins.
Epigenetics is the study of heritable changes in gene function that occur without a change in the underlying DNA sequence. These changes can be caused by various mechanisms such as DNA methylation, histone modification, and non-coding RNA molecules. Epigenetic changes can be influenced by various factors including age, environment, lifestyle, and disease state.
Genetic epigenesis specifically refers to the study of how genetic factors influence these epigenetic modifications. Genetic variations between individuals can lead to differences in epigenetic patterns, which in turn can contribute to phenotypic variation and susceptibility to diseases. For example, certain genetic variants may predispose an individual to develop cancer, and environmental factors such as smoking or exposure to chemicals can interact with these genetic variants to trigger epigenetic changes that promote tumor growth.
Overall, the field of genetic epigenesis aims to understand how genetic and environmental factors interact to regulate gene expression and contribute to disease susceptibility.
5-Methylcytosine (5mC) is a chemical modification of the nucleotide base cytosine in DNA, where a methyl group (-CH3) is added to the 5th carbon atom of the cytosine ring. This modification is catalyzed by DNA methyltransferase enzymes and plays an essential role in epigenetic regulation of gene expression, genomic imprinting, X-chromosome inactivation, and suppression of transposable elements in eukaryotic cells. Abnormal DNA methylation patterns have been associated with various diseases, including cancer.