scholarly journals A class I odorant receptor enhancer shares a functional motif with class II enhancers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tetsuo Iwata ◽  
Satoshi Tomeoka ◽  
Junji Hirota
Keyword(s):  
Molecular Mechanisms ◽  
Odorant Receptor ◽  
Regulatory Element ◽  
Mammalian Species ◽  
Class Ii ◽  
Class I ◽  
Enhancer Activity ◽  
Functional Motif ◽  
Functional Region ◽  
Or Genes

AbstractIn the mouse, 129 functional class I odorant receptor (OR) genes reside in a ~ 3 megabase huge gene cluster on chromosome 7. The J element, a long-range cis-regulatory element governs the singular expression of class I OR genes by exerting its effect over the whole cluster. To elucidate the molecular mechanisms underlying class I-specific enhancer activity of the J element, we analyzed the J element sequence to determine the functional region and essential motif. The 430-bp core J element, that is highly conserved in mammalian species from the platypus to humans, contains a class I-specific conserved motif of AAACTTTTC, multiple homeodomain sites, and a neighboring O/E-like site, as in class II OR-enhancers. A series of transgenic reporter assays demonstrated that the class I-specific motif is not essential, but the 330-bp core J-H/O containing the homeodomain and O/E-like sites is necessary and sufficient for class I-specific enhancer activity. Further motif analysis revealed that one of homeodomain sequence is the Greek Islands composite motif of the adjacent homeodomain and O/E-like sequences, and mutations in the composite motif abolished or severely reduced class I-enhancer activity. Our results demonstrate that class I and class II enhancers share a functional motif for their enhancer activity.

In vivo function of regulatory DNA sequence elements of a major histocompatibility complex class I gene

1992 ◽  
Vol 12 (7) ◽  
pp. 3078-3086
Author(s):  
J E Maguire ◽  
W I Frels ◽  
J C Richardson ◽  
J D Weissman ◽  
D S Singer
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Regulatory Element ◽  
Class I ◽  
Lymphoid Tissues ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Enhancer Activity ◽  
Tissue Specific ◽  
Histocompatibility Complex

Major histocompatibility complex class I genes are expressed in nearly all somatic tissues, although their level of expression varies. By analysis of a set of promoter deletion mutants introduced into transgenic mice, a complex regulatory element, consisting of overlapping enhancer and silencer activities, is demonstrated to function as a tissue-specific regulator of class I expression. The enhancer activity predominates in lymphoid tissues but not in nonlymphoid tissues. In contrast to the tissue-specific functions of the complex regulatory element, a second novel silencer element is shown to function in both lymphoid and nonlymphoid tissues. The complement of DNA-binding factors in different cell lines is shown to correlate with the levels of class I expression.

scholarly journals A long-range cis-regulatory element for class I odorant receptor genes

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Tetsuo Iwata ◽  
Yoshihito Niimura ◽  
Chizuru Kobayashi ◽  
Daichi Shirakawa ◽  
Hikoyu Suzuki ◽  
...  
Keyword(s):  
Long Range ◽  
Odorant Receptor ◽  
Regulatory Element ◽  
Class I

scholarly journals Transcriptome and DNA Methylation Analyses of the Molecular Mechanisms Underlying with Longissimus dorsi Muscles at Different Stages of Development in the Polled Yak

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 970 ◽  
Author(s):  
Ma ◽  
Jia ◽  
Chu ◽  
Fu ◽  
Lei ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Methylation Status ◽  
Muscle Growth ◽  
Class Ii ◽  
Epigenetic Mechanism ◽  
Class I ◽  
Longissimus Dorsi ◽  
Growth Stages

DNA methylation modifications are implicated in many biological processes. As the most common epigenetic mechanism DNA methylation also affects muscle growth and development. The majority of previous studies have focused on different varieties of yak, but little is known about the epigenetic regulation mechanisms in different age groups of animals. The development of muscles in the different stages of yak growth remains unclear. In this study, we selected the longissimus dorsi muscle tissue at three different growth stages of the yak, namely, 90-day-old fetuses (group E), six months old (group M), and three years old (group A). Using RNA-Seq transcriptome sequencing and methyl-RAD whole-genome methylation sequencing technology, changes in gene expression levels and DNA methylation status throughout the genome were investigated during the stages of yak development. Each group was represented by three biological replicates. The intersections of expression patterns of 7694 differentially expressed genes (DEGs) were identified (padj < 0.01, |log2FC| > 1.2) at each of the three developmental periods. Time-series expression profile clustering analysis indicated that the DEGs were significantly arranged into eight clusters which could be divided into two classes (padj < 0.05), class I profiles that were downregulated and class II profiles that were upregulated. Based on this cluster analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that DEGs from class I profiles were significantly (padj < 0.05) enriched in 21 pathways, the most enriched pathway being the Axon guidance signaling pathway. DEGs from the class II profile were significantly enriched in 58 pathways, the pathway most strongly enriched being Metabolic pathway. After establishing the methylation profiles of the whole genomes, and using two groups of comparisons, the three combinations of groups (M-vs.-E, M-vs.-A, A-vs.-E) were found to have 1344, 822, and 420 genes, respectively, that were differentially methylated at CCGG sites and 2282, 3056, and 537 genes, respectively, at CCWGG sites. The two sets of data were integrated and the negative correlations between DEGs and differentially methylated promoters (DMPs) analyzed, which confirmed that TMEM8C, IGF2, CACNA1S and MUSTN1 were methylated in the promoter region and that expression of the modified genes was negatively correlated. Interestingly, these four genes, from what was mentioned above, perform vital roles in yak muscle growth and represent a reference for future genomic and epigenomic studies in muscle development, in addition to enabling marker-assisted selection of growth traits.

scholarly journals Developmental and tissue-specific expression of nuclear proteins that bind the regulatory element of the major histocompatibility complex class I gene.

1989 ◽  
Vol 169 (4) ◽  
pp. 1309-1321 ◽  
Author(s):  
P A Burke ◽  
S Hirschfeld ◽  
Y Shirayoshi ◽  
J W Kasik ◽  
K Hamada ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mhc Class I ◽  
Regulatory Element ◽  
Binding Activity ◽  
Class I ◽  
Specific Expression ◽  
Enhancer Activity ◽  
Region I ◽  
Region Ii ◽  
I Gene

Expression of MHC class I genes varies according to developmental stage and type of tissues. To study the basis of class I gene regulation in tissues in vivo, we examined binding of nuclear proteins to the conserved cis sequence of the murine H-2 gene, class I regulatory element (CRE), which contains two independent factor-binding sites, region I and region II. In gel mobility shift analyses we found that extracts from adult tissues that express class I genes, such as spleen and liver, had binding activity to region I. In contrast, extracts from brain, which does not express class I genes, did not show region I binding activity. In addition, fetal tissues that express class I gene at very low levels, also did not reveal region I binding activity. Binding activity to region I became detectable during the neonatal period when class I gene expression sharply increases. Most of these tissues showed binding activity to region II, irrespective of class I gene expression. Although region II contained a sequence similar to the AP-1 recognition site, AP-1 was not responsible for the region II binding activity detected in this work. These results illustrate a correlation between region I binding activity and developmental and tissue-specific expression of MHC class I genes. The CRE exerts an enhancer-like activity in cultured fibroblasts. We evaluated the significance of each factor binding to CRE. Single 2-bp mutations were introduced into the CRE by site-directed mutagenesis and the ability of each mutant to elicit the enhancer activity was tested in transient CAT assays. A mutation that eliminated region I protein binding greatly impaired enhancer activity. A mutation that eliminated region II binding also caused a lesser but measurable effect. We conclude that region I and region II are both capable of enhancing transcription of the class I gene. These results indicate that in vivo regulation of MHC class I gene expression is mediated by binding of trans-acting factors to the CRE.

scholarly journals Phosphoinositide 3-Kinase C2β Regulates Cytoskeletal Organization and Cell Migration via Rac-dependent Mechanisms

2006 ◽  
Vol 17 (9) ◽  
pp. 3729-3744 ◽  
Author(s):  
Roy M. Katso ◽  
Olivier E. Pardo ◽  
Andrea Palamidessi ◽  
Clemens M. Franz ◽  
Marin Marinov ◽  
...  
Keyword(s):  
Cell Migration ◽  
Molecular Mechanisms ◽  
Egf Receptor ◽  
Human Tumor ◽  
Class Ii ◽  
Dominant Negative ◽  
Class I ◽  
Membrane Ruffling ◽  
And Migration ◽  
Phosphoinositide 3 Kinase

Receptor-linked class I phosphoinositide 3-kinases (PI3Ks) induce assembly of signal transduction complexes through protein–protein and protein–lipid interactions that mediate cell proliferation, survival, and migration. Although class II PI3Ks have the potential to make the same phosphoinositides as class I PI3Ks, their precise cellular role is currently unclear. In this report, we demonstrate that class II phosphoinositide 3-kinase C2β (PI3KC2β) associates with the Eps8/Abi1/Sos1 complex and is recruited to the EGF receptor as part of a multiprotein signaling complex also involving Shc and Grb2. Increased expression of PI3KC2β stimulated Rac activity in A-431 epidermoid carcinoma cells, resulting in enhanced membrane ruffling and migration speed of the cells. Conversely, expression of dominant negative PI3KC2β reduced Rac activity, membrane ruffling, and cell migration. Moreover, PI3KC2β-overexpressing cells were protected from anoikis and displayed enhanced proliferation, independently of Rac function. Taken together, these findings suggest that PI3KC2β regulates the migration and survival of human tumor cells by distinct molecular mechanisms.

scholarly journals The evolutionary dynamics of the odorant receptor gene family in corbiculate bees

2017 ◽  
Author(s):  
Philipp Brand ◽  
Santiago R. Ramírez
Keyword(s):  
Positive Selection ◽  
Gene Family ◽  
Molecular Mechanisms ◽  
Odorant Receptor ◽  
Floral Resources ◽  
Specific Gene ◽  
Repertoire Size ◽  
Or Gene ◽  
Corbiculate Bees ◽  
Or Genes

AbstractInsects rely on chemical information to locate food, choose mates, and detect potential predators. It has been hypothesized that adaptive changes in the olfactory system facilitated the diversification of numerous insect lineages. For instance, evolutionary changes of Odorant Receptor (OR) genes often occur in parallel with modifications in life history strategies. Corbiculate bees display a diverse array of behaviors that are controlled through olfaction, including varying degrees of social organization, and manifold associations with floral resources. Here we investigated the molecular mechanisms driving the evolution of the OR gene family in corbiculate bees in comparison to other chemosensory gene families. Our results indicate that the genomic organization of the OR gene family has remained highly conserved for approximately 80 million years, despite exhibiting major changes in repertoire size among bee lineages. Moreover, the evolution of OR genes appears to be driven mostly by lineage-specific gene duplications in few genomic regions that harbor large numbers of OR genes. A selection analysis revealed that OR genes evolve under positive selection, with the strongest signals detected in recently duplicated copies. Our results indicate that chromosomal translocations had a minimal impact on OR evolution, and instead local molecular mechanisms appear to be main drivers of OR repertoire size. Our results provide empirical support to the longstanding hypothesis that positive selection shaped the diversification of the OR gene family. Together, our results shed new light on the molecular mechanisms underlying the evolution of olfaction in insects.

scholarly journals A Two-Step, PU.1-Dependent Mechanism for Developmentally Regulated Chromatin Remodeling and Transcription of the c-fms Gene

2006 ◽  
Vol 27 (3) ◽  
pp. 878-887 ◽  
Author(s):  
Hanna Krysinska ◽  
Maarten Hoogenkamp ◽  
Richard Ingram ◽  
Nicola Wilson ◽  
Hiromi Tagoh ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Gene Activation ◽  
Myeloid Cell ◽  
Developmentally Regulated ◽  
Enhancer Activity ◽  
Hematopoietic Stem ◽  
Multipotent Progenitors ◽  
Ets Family

ABSTRACT Hematopoietic stem cells and multipotent progenitors exhibit low-level transcription and partial chromatin reorganization of myeloid cell-specific genes including the c-fms (csf1R) locus. Expression of the c-fms gene is dependent on the Ets family transcription factor PU.1 and is upregulated during myeloid differentiation, enabling committed macrophage precursors to respond to colony-stimulating factor 1. To analyze molecular mechanisms underlying the transcriptional priming and developmental upregulation of the c-fms gene, we have utilized myeloid progenitors lacking the transcription factor PU.1. PU.1 can bind to sites in both the c-fms promoter and the c-fms intronic regulatory element (FIRE enhancer). Unlike wild-type progenitors, the PU.1−/− cells are unable to express c-fms or initiate macrophage differentiation. When PU.1 was reexpressed in mutant progenitors, the chromatin structure of the c-fms promoter was rapidly reorganized. In contrast, assembly of transcription factors at FIRE, acquisition of active histone marks, and high levels of c-fms transcription occurred with significantly slower kinetics. We demonstrate that the reason for this differential activation was that PU.1 was required to promote induction and binding of a secondary transcription factor, Egr-2, which is important for FIRE enhancer activity. These data suggest that the c-fms promoter is maintained in a primed state by PU.1 in progenitor cells and that at FIRE PU.1 functions with another transcription factor to direct full activation of the c-fms locus in differentiated myeloid cells. The two-step mechanism of developmental gene activation that we describe here may be utilized to regulate gene activity in a variety of developmental pathways.

scholarly journals Transmembrane channel-like (tmc) gene regulates Drosophila larval locomotion

2016 ◽  
Vol 113 (26) ◽  
pp. 7243-7248 ◽  
Author(s):  
Yanmeng Guo ◽  
Yuping Wang ◽  
Wei Zhang ◽  
Shan Meltzer ◽  
Damiano Zanini ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Sensory Feedback ◽  
Molecular Mechanisms ◽  
Class Ii ◽  
Class I ◽  
Larval Body ◽  
Functional Conservation ◽  
Transmembrane Channel ◽  
Mutant Phenotypes ◽  
Bending Response

Drosophila larval locomotion, which entails rhythmic body contractions, is controlled by sensory feedback from proprioceptors. The molecular mechanisms mediating this feedback are little understood. By using genetic knock-in and immunostaining, we found that the Drosophila melanogaster transmembrane channel-like (tmc) gene is expressed in the larval class I and class II dendritic arborization (da) neurons and bipolar dendrite (bd) neurons, both of which are known to provide sensory feedback for larval locomotion. Larvae with knockdown or loss of tmc function displayed reduced crawling speeds, increased head cast frequencies, and enhanced backward locomotion. Expressing Drosophila TMC or mammalian TMC1 and/or TMC2 in the tmc-positive neurons rescued these mutant phenotypes. Bending of the larval body activated the tmc-positive neurons, and in tmc mutants this bending response was impaired. This implicates TMC’s roles in Drosophila proprioception and the sensory control of larval locomotion. It also provides evidence for a functional conservation between Drosophila and mammalian TMCs.

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