scholarly journals The Stage-regulated Expression ofLeishmania mexicanaCPB Cysteine Proteases Is Mediated by an Intercistronic Sequence Element

2001 ◽  
Vol 276 (50) ◽  
pp. 47061-47069 ◽  
Author(s):  
Darren R. Brooks ◽  
Hubert Denise ◽  
Gareth D. Westrop ◽  
Graham H. Coombs ◽  
Jeremy C. Mottram
Keyword(s):  
Untranslated Region ◽  
Regulatory Element ◽  
Cysteine Proteases ◽  
Specific Gene ◽  
Base Pairs ◽  
Specific Expression ◽  
Sequence Element ◽  
Repeat Units ◽  
Regulated Expression ◽  
Specific Stage

The tandemly arrangedCPBgenes ofLeishmania mexicanaare polycistronically transcribed and encode cysteine proteases that are differentially stage-specific;CPB1andCPB2are expressed predominantly in metacyclics, whereasCPB3–CPB18are expressed mainly in amastigotes. The mechanisms responsible for this differential expression have been studied via gene analysis and re-integration of individualCPBgenes, and variants thereof, into aCPB-deficient parasite mutant. Comparison of the nucleotide sequences of the repeat units ofCPB1andCPB2withCPB2.8(typical ofCPB3–CPB18) revealed two major regions of divergence as follows: one of 258 base pairs (bp) corresponding to the C-terminal extension of CPB2.8; another, designated InS, of 120 bp, with insertions totaling 57 bp, localized to the intercistronic region downstream ofCPB1andCPB2. Cell lines expressingCPB2.8orCPB2with the 3′-untranslated region and intercistronic sequence ofCPB2.8showed up-regulation in amastigotes. Conversely, metacyclic-specific expression occurred withCPB2orCPB2.8with the 3′-untranslated region and intercistronic sequence ofCPB2. Moreover, the InS down-regulated expression in amastigotes of a reporter gene integrated into theCPBlocus. It is proposed that the InS mediates metacyclic-specific stage-regulated expression ofCPBby affecting the maturation of polycistronic pre-mRNA. This is the first well definedcis-regulatory element implicated in post-transcriptional stage-specific gene expression inLeishmania.

scholarly journals A Negative Regulatory Element Controls mRNA Abundance of the Leishmania mexicana Paraflagellar Rod Gene PFR2

2003 ◽  
Vol 2 (5) ◽  
pp. 1009-1017 ◽  
Author(s):  
Krishna K. Mishra ◽  
Timothy R. Holzer ◽  
Landon L. Moore ◽  
Jonathan H. LeBowitz
Keyword(s):  
Life Cycle ◽  
Untranslated Region ◽  
Regulatory Element ◽  
Constitutive Expression ◽  
Mrna Abundance ◽  
Mrna Levels ◽  
Leishmania Mexicana ◽  
Specific Expression ◽  
Negative Regulatory Element ◽  
Regulated Expression

ABSTRACT The Leishmania mexicana PFR2 locus encodes a component of the paraflagellar rod (PFR), a flagellar structure found only in the insect stage of the life cycle. PFR2 mRNA levels are 10-fold lower in the mammalian stage than in the insect stage. Nuclear run-on experiments indicate that the change in PFR2 mRNA abundance is achieved posttranscriptionally. Deletion and block substitution analysis of the entire 1,400-nucleotide 3′ untranslated region (UTR) of PFR2C led to the identification of a regulatory element contained within 10 nucleotides of the 3′ UTR, termed the PFR regulatory element (PRE), that is necessary for the 10-fold regulation of PFR2 mRNA levels. Comparison of the half-lives of PFR2 transcripts, identical except for the presence or absence of the PRE, revealed that the PRE acts by destabilizing the PFR2 mRNA in amastigotes. The PRE was inserted into a construct which directs the constitutive expression of a chimeric PFR2 transcript. Insertion of the PRE resulted in regulated expression of this transcript, demonstrating that the regulatory element is sufficient for promastigote-specific expression. Since the PRE is present in the 3′ UTR of all L. mexicana PFR genes examined so far, we propose that it serves a means of coordinating expression of PFR genes.

Identification of a signal transduction response sequence element necessary for induction of a Dictyostelium discoideum gene by extracellular cyclic AMP

1989 ◽  
Vol 9 (11) ◽  
pp. 4660-4669
Author(s):  
J Pavlovic ◽  
B Haribabu ◽  
R P Dottin
Keyword(s):  
Signal Transduction ◽  
Cyclic Amp ◽  
Dictyostelium Discoideum ◽  
Regulatory Element ◽  
Response Sequence ◽  
Base Pairs ◽  
Camp Response Element ◽  
Sequence Element ◽  
Cis Acting ◽  
Gene Coding

The signal transduction pathways that lead to gene induction are being intensively investigated in Dictyostelium discoideum. We have identified by deletion and transformation analysis a sequence element necessary for induction of a gene coding for uridine diphosphoglucose pyrophosphorylase (UDPGP1) of D. discoideum in response to extracellular cyclic AMP (cAMP). This regulatory element is located 380 base pairs upstream of the transcription start site and contains a G+C-rich partially palindromic sequence. It is not required for transcription per se but is required for induction of the gene in response to the stimulus of extracellular cAMP. The cAMP response sequence is also required for induction of the gene during normal development. A second A+T-rich cis-acting region located immediately downstream of the cAMP response sequence appears to be essential for the basal level of expression of the UDPGP1 gene. The position of the cAMP response element coincides with a DNase I-hypersensitive site that is observed when the UDPGP1 gene is actively transcribed.

scholarly journals Positive and negative elements regulate a melanocyte-specific promoter

1992 ◽  
Vol 12 (8) ◽  
pp. 3653-3662
Author(s):  
P Lowings ◽  
U Yavuzer ◽  
C R Goding
Keyword(s):  
Protein Interactions ◽  
Regulatory Element ◽  
Basal Layer ◽  
Regulatory Elements ◽  
Hair Follicles ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

Melanocytes are specialized cells residing in the hair follicles, the eye, and the basal layer of the human epidermis whose primary function is the production of the pigment melanin, giving rise to skin, hair, and eye color. Melanogenesis, a process unique to melanocytes that involves the processing of tyrosine by a number of melanocyte-specific enzymes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), occurs only after differentiation from the melanocyte precursor, the melanoblast. In humans, melanogenesis is inducible by UV irradiation, with melanin being transferred from the melanocyte in the epidermis to the surrounding keratinocytes as protection from UV-induced damage. Excessive exposure to UV, however, is the primary cause of malignant melanoma, an increasingly common and highly aggressive disease. As an initial approach to understanding the regulation of melanocyte differentiation and melanocyte-specific transcription, we have isolated the gene encoding TRP-1 and examined the cis- and trans-acting factors required for cell-type-specific expression. We find that the TRP-1 promoter comprises both positive and negative regulatory elements which confer efficient expression in a TRP-1-expressing, pigmented melanoma cell line but not in NIH 3T3 or JEG3 cells and that a minimal promoter extending between -44 and +107 is sufficient for cell-type-specific expression. Assays for DNA-protein interactions coupled with extensive mutagenesis identified three factors, whose binding correlated with the function of two positive and one negative regulatory element. One of these factors, termed M-box-binding factor 1, binds to an 11-bp motif, the M box, which acts as a positive regulatory element both in TRP-1-expressing and -nonexpressing cell lines, despite being entirely conserved between the melanocyte-specific tyrosinase and TRP-1 promoters. The possible mechanisms underlying melanocyte-specific gene expression are discussed.

Epigenetic Remodeling in Innate Immunity and Inflammation

2021 ◽  
Vol 39 (1) ◽  
Author(s):  
Qian Zhang ◽  
Xuetao Cao
Keyword(s):  
Gene Expression ◽  
Innate Immunity ◽  
Regulatory Element ◽  
Expression Patterns ◽  
Innate Immune ◽  
Annual Review ◽  
Specific Gene ◽  
Publication Date ◽  
Specific Expression ◽  
Epigenetic Remodeling

The innate immune response is a rapid response to pathogens or danger signals. It is precisely activated not only to efficiently eliminate pathogens but also to avoid excessive inflammation and tissue damage. cis-Regulatory element–associated chromatin architecture shaped by epigenetic factors, which we define as the epiregulome, endows innate immune cells with specialized phenotypes and unique functions by establishing cell-specific gene expression patterns, and it also contributes to resolution of the inflammatory response. In this review, we focus on two aspects: ( a) how niche signals during lineage commitment or following infection and pathogenic stress program epiregulomes by regulating gene expression levels, enzymatic activities, or gene-specific targeting of chromatin modifiers and ( b) how the programed epiregulomes in turn mediate regulation of gene-specific expression, which contributes to controlling the development of innate cells, or the response to infection and inflammation, in a timely manner. We also discuss the effects of innate immunometabolic rewiring on epiregulomes and speculate on several future challenges to be encountered during the exploration of the master regulators of epiregulomes in innate immunity and inflammation. Expected final online publication date for the Annual Review of Immunology, Volume 39 is April 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Positive and negative elements regulate a melanocyte-specific promoter.

1992 ◽  
Vol 12 (8) ◽  
pp. 3653-3662 ◽  
Author(s):  
P Lowings ◽  
U Yavuzer ◽  
C R Goding
Keyword(s):  
Protein Interactions ◽  
Regulatory Element ◽  
Basal Layer ◽  
Regulatory Elements ◽  
Hair Follicles ◽  
Specific Gene ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

Melanocytes are specialized cells residing in the hair follicles, the eye, and the basal layer of the human epidermis whose primary function is the production of the pigment melanin, giving rise to skin, hair, and eye color. Melanogenesis, a process unique to melanocytes that involves the processing of tyrosine by a number of melanocyte-specific enzymes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), occurs only after differentiation from the melanocyte precursor, the melanoblast. In humans, melanogenesis is inducible by UV irradiation, with melanin being transferred from the melanocyte in the epidermis to the surrounding keratinocytes as protection from UV-induced damage. Excessive exposure to UV, however, is the primary cause of malignant melanoma, an increasingly common and highly aggressive disease. As an initial approach to understanding the regulation of melanocyte differentiation and melanocyte-specific transcription, we have isolated the gene encoding TRP-1 and examined the cis- and trans-acting factors required for cell-type-specific expression. We find that the TRP-1 promoter comprises both positive and negative regulatory elements which confer efficient expression in a TRP-1-expressing, pigmented melanoma cell line but not in NIH 3T3 or JEG3 cells and that a minimal promoter extending between -44 and +107 is sufficient for cell-type-specific expression. Assays for DNA-protein interactions coupled with extensive mutagenesis identified three factors, whose binding correlated with the function of two positive and one negative regulatory element. One of these factors, termed M-box-binding factor 1, binds to an 11-bp motif, the M box, which acts as a positive regulatory element both in TRP-1-expressing and -nonexpressing cell lines, despite being entirely conserved between the melanocyte-specific tyrosinase and TRP-1 promoters. The possible mechanisms underlying melanocyte-specific gene expression are discussed.

scholarly journals Tissue-specific gene expression in the pituitary: the glycoprotein hormone alpha-subunit gene is regulated by a gonadotrope-specific protein.

1992 ◽  
Vol 12 (5) ◽  
pp. 2143-2153 ◽  
Author(s):  
F Horn ◽  
J J Windle ◽  
K M Barnhart ◽  
P L Mellon
Keyword(s):  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Alpha Subunit ◽  
Specific Factor ◽  
Specific Gene ◽  
Homeodomain Protein ◽  
Subunit Gene ◽  
Glycoprotein Hormone ◽  
Specific Expression ◽  
Tissue Specific

The molecular mechanisms for the development of multiple distinct endocrine cell types in the anterior pituitary have been an area of intensive investigation. Though the homeodomain protein Pit-1/GHF-1 is known to be involved in differentiation of the somatotrope and lactotrope lineages, which produce growth hormone and prolactin, respectively, little is known of the transcriptional regulators important for the gonadotrope cell lineage, which produces the glycoprotein hormones luteinizing hormone and follicle-stimulating hormone. Using transgenic mice and transfection into a novel gonadotrope lineage cell line, we have identified a regulatory element that confers gonadotrope-specific expression to the glycoprotein hormone alpha-subunit gene. A tissue-specific factor that binds to this element is purified and characterized as a 54-kDa protein which is present uniquely in cells of the gonadotrope lineage and is not Pit-1/GHF-1. The human and equine alpha-subunit genes are also expressed in placental cells. However, the previously characterized placental transcription factors designated TSEB and alpha-ACT are not found in the pituitary gonadotrope cells, indicating that independent mechanisms confer expression of these genes in the two different tissues.

scholarly journals Identification of a signal transduction response sequence element necessary for induction of a Dictyostelium discoideum gene by extracellular cyclic AMP.

1989 ◽  
Vol 9 (11) ◽  
pp. 4660-4669 ◽  
Author(s):  
J Pavlovic ◽  
B Haribabu ◽  
R P Dottin
Keyword(s):  
Signal Transduction ◽  
Cyclic Amp ◽  
Dictyostelium Discoideum ◽  
Regulatory Element ◽  
Response Sequence ◽  
Base Pairs ◽  
Camp Response Element ◽  
Sequence Element ◽  
Cis Acting ◽  
Gene Coding

The signal transduction pathways that lead to gene induction are being intensively investigated in Dictyostelium discoideum. We have identified by deletion and transformation analysis a sequence element necessary for induction of a gene coding for uridine diphosphoglucose pyrophosphorylase (UDPGP1) of D. discoideum in response to extracellular cyclic AMP (cAMP). This regulatory element is located 380 base pairs upstream of the transcription start site and contains a G+C-rich partially palindromic sequence. It is not required for transcription per se but is required for induction of the gene in response to the stimulus of extracellular cAMP. The cAMP response sequence is also required for induction of the gene during normal development. A second A+T-rich cis-acting region located immediately downstream of the cAMP response sequence appears to be essential for the basal level of expression of the UDPGP1 gene. The position of the cAMP response element coincides with a DNase I-hypersensitive site that is observed when the UDPGP1 gene is actively transcribed.

Tissue-specific gene expression in the pituitary: the glycoprotein hormone alpha-subunit gene is regulated by a gonadotrope-specific protein

1992 ◽  
Vol 12 (5) ◽  
pp. 2143-2153
Author(s):  
F Horn ◽  
J J Windle ◽  
K M Barnhart ◽  
P L Mellon
Keyword(s):  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Alpha Subunit ◽  
Specific Factor ◽  
Specific Gene ◽  
Homeodomain Protein ◽  
Subunit Gene ◽  
Glycoprotein Hormone ◽  
Specific Expression ◽  
Tissue Specific

The molecular mechanisms for the development of multiple distinct endocrine cell types in the anterior pituitary have been an area of intensive investigation. Though the homeodomain protein Pit-1/GHF-1 is known to be involved in differentiation of the somatotrope and lactotrope lineages, which produce growth hormone and prolactin, respectively, little is known of the transcriptional regulators important for the gonadotrope cell lineage, which produces the glycoprotein hormones luteinizing hormone and follicle-stimulating hormone. Using transgenic mice and transfection into a novel gonadotrope lineage cell line, we have identified a regulatory element that confers gonadotrope-specific expression to the glycoprotein hormone alpha-subunit gene. A tissue-specific factor that binds to this element is purified and characterized as a 54-kDa protein which is present uniquely in cells of the gonadotrope lineage and is not Pit-1/GHF-1. The human and equine alpha-subunit genes are also expressed in placental cells. However, the previously characterized placental transcription factors designated TSEB and alpha-ACT are not found in the pituitary gonadotrope cells, indicating that independent mechanisms confer expression of these genes in the two different tissues.

scholarly journals Identification of a Novel cis-Element in the 3′-Untranslated Region of Mammalian Peptidylglycine α-Amidating Monooxygenase Messenger Ribonucleic Acid

Endocrinology ◽  
1998 ◽  
Vol 139 (3) ◽  
pp. 894-904 ◽  
Author(s):  
Sandrine Fraboulet ◽  
Françoise Boudouresque ◽  
Christine Delfino ◽  
L’Houcine Ouafik
Keyword(s):  
Binding Site ◽  
Protein Complex ◽  
Untranslated Region ◽  
Tumor Cell Line ◽  
Binding Activity ◽  
Messenger Rnas ◽  
Specific Expression ◽  
Sequence Element ◽  
Messenger Ribonucleic Acid ◽  
Cis Element

Peptidylglycine α-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the COOH-terminal α-amidation of peptidylglycine substrates, yielding amidated products. Growing evidence suggests that the metabolism of PAM messenger RNAs (mRNAs) can be regulated within the cytoplasm. To understand the mechanisms controlling the metabolism of PAM mRNAs, we sought to identify cis elements of the 3′-untranslated region (3′-UTR) of PAM mRNA that are recognized by cytoplasmic factors. From gel retardation assays, one sequence element is shown to form a specific RNA-protein complex. The protein-binding site of the complex was determined by ribonuclease T1 mapping, by blocking the putative binding site with antisense oligonucleotide, and by competition assays. Using 3′-end-labeled RNA in gel shift and UV cross-linking analyses, we detected in the 3′-UTR a novel 20-nucleotide cis element that interacted with a widely distributed cellular cytosolic protease-sensitive factor(s) to form a 60-kDa PAM mRNA-binding protein complex. The binding activity was redox sensitive. Tissue distribution of the protein in the rat showed a marked tissue-specific expression, with ovary, testis, lung, heart septum, anterior pituitary and hypothalamus containing large amounts compared with liver, ventricle, atrium, and neurointermediate lobe. No binding activity was detectable in pancreas, intestine, or kidney extracts. Northwestern blot analysis of AtT-20 (mouse corticotrope tumor cell line) cytoplasmic extracts revealed a protein of 46 kDa. Thus, we have identified a widely distributed cellular protein that binds to a conserved domain within the 3′-UTR of PAM mRNA from many animal species. Although these data suggest that cis element-binding activity could be a cytoplasmic regulator of PAM mRNA metabolism, the functional consequences of this binding remain to be determined.

scholarly journals A DNA-bending protein interacts with an essential upstream regulatory element of the human embryonic beta-like globin gene.

1996 ◽  
Vol 16 (3) ◽  
pp. 829-838 ◽  
Author(s):  
M A Dyer ◽  
R Naidoo ◽  
R J Hayes ◽  
C J Larson ◽  
G L Verdine ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Globin Gene ◽  
Gene Promoter ◽  
Developmental State ◽  
Biochemical Properties ◽  
Erythroid Cell ◽  
Control Element ◽  
Specific Gene ◽  
Globin Genes ◽  
Specific Expression

The mammalian beta-like globin gene family has served as an important model system for analysis of tissue- and developmental state-specific gene regulation. Although the activities of a number of regulatory proteins have been implicated in the erythroid cell-specific transcription of globin genes, the mechanisms that restrict their expression to discrete stages of development are less well understood. We have previously identified a novel regulatory element (PRE II) upstream from the human embryonic beta-like globin gene (epsilon) that synergizes with other sequences to confer tissue- and stage-specific expression on a minimal epsilon-globin gene promoter in cultured embryonic erythroid cells. Binding of an erythroid nuclear protein (PRE II-binding factor [PRE-IIBF]) to the PRE II control element is required for promoter activation. Here we report on some of the biochemical properties of PREIIBF, including the characterization of its specificity and affinity for DNA. The embryonic and adult forms of PREIIBF recognize their cognate sequences with identical specificities, supporting our earlier conclusion that they are very similar proteins. PREIIBF binds DNA as a single polypeptide with an Mr of approximately 80,000 to 85,000 and introduces a bend into the target DNA molecule. These results suggest a mechanism by which PREIIBF may contribute to the regulation of the embryonic beta-like globin gene within the context of a complex locus.

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