scholarly journals Interactions of Sox10 and Egr2 in myelin gene regulation

2007 ◽  
Vol 3 (4) ◽  
pp. 377-387 ◽  
Author(s):  
Erin A. Jones ◽  
Sung-Wook Jang ◽  
Gennifer M. Mager ◽  
Li-Wei Chang ◽  
Rajini Srinivasan ◽  
...  
Keyword(s):  
Binding Sites ◽  
Basic Protein ◽  
Developmental Regulation ◽  
Regulatory Element ◽  
Enhancer Element ◽  
First Intron ◽  
Genes Encoding ◽  
Myelin Associated Glycoprotein ◽  
Protein Zero ◽  
Myelin Gene

AbstractMyelination in the PNS is accompanied by a large induction of the myelin protein zero (Mpz) gene to produce the most abundant component in peripheral myelin. Analyses of knockout mice have shown that the EGR2/Krox20 and SOX10 transcription factors are required for Mpz expression. Our recent work has shown that the dominant EGR2 mutations associated with human peripheral neuropathies cause disruption of EGR2/SOX10 synergy at specific sites, including a conserved enhancer element in the first intron of the Mpz gene. Further investigation of Egr2/Sox10 interactions reveals that activation of the Mpz intron element by Egr2 requires both Sox10-binding sites. In addition, both Egr1 and Egr3 cooperate with Sox10 to activate this element, which indicates that this capacity is conserved among Egr family members. Finally, a conserved composite structure of Egr2/Sox10-binding sites in the genes encoding Mpz, myelin-associated glycoprotein and myelin basic protein genes was used to screen for similar modules in other myelin genes, revealing a potential regulatory element in the periaxin gene. Overall, these results elucidate a working model for developmental regulation of Mpz expression, several facets of which extend to regulation of other peripheral myelin genes.

scholarly journals A complex regulatory element from the yeast gene ENO2 modulates GCR1-dependent transcriptional activation

1993 ◽  
Vol 13 (4) ◽  
pp. 2623-2633
Author(s):  
C E Willett ◽  
C M Gelfman ◽  
M J Holland
Keyword(s):  
Binding Site ◽  
Transcriptional Activation ◽  
Binding Sites ◽  
Regulatory Element ◽  
Enhancer Element ◽  
Cis Acting ◽  
Genes Encoding ◽  
High Level ◽  
Yeast Genes ◽  
Yeast Enolase

The GCR1 gene product is required for maximal transcription of many yeast genes including genes encoding glycolytic enzymes. Transcription of the yeast enolase gene ENO2 is reduced 50-fold in strains carrying a gcr1 null mutation. cis-acting sequences that are sufficient for GCR1-dependent regulation of ENO2 expression were identified by using an enhancerless CYC1 promoter which is not normally dependent on GCR1 for expression. A 60-bp ENO2 sequence that was sufficient to provide high-level, GCR1-dependent transcriptional activation of the CYC1 promoter was identified. This 60-bp element could be subdivided into a 30-bp sequence containing a novel RAP1-binding site and a GCR1-binding site which did not activate CYC1 transcription and a 30-bp sequence containing a novel enhancer element that conferred moderate levels of GCR1-independent transcriptional activation. The 60-bp CGCR1-dependent upstream activator sequence is located immediately downstream from previously mapped overlapping binding sites for the regulatory proteins ABFI and RAP1. Evidence is presented that the overlapping ABFI- and RAP1-binding sites function together with sequences that bind GCR1 and RAP1 to stage transcriptional activation of ENO2 expression.

scholarly journals A complex regulatory element from the yeast gene ENO2 modulates GCR1-dependent transcriptional activation.

1993 ◽  
Vol 13 (4) ◽  
pp. 2623-2633 ◽  
Author(s):  
C E Willett ◽  
C M Gelfman ◽  
M J Holland
Keyword(s):  
Binding Site ◽  
Transcriptional Activation ◽  
Binding Sites ◽  
Regulatory Element ◽  
Enhancer Element ◽  
Cis Acting ◽  
Genes Encoding ◽  
High Level ◽  
Yeast Genes ◽  
Yeast Enolase

The GCR1 gene product is required for maximal transcription of many yeast genes including genes encoding glycolytic enzymes. Transcription of the yeast enolase gene ENO2 is reduced 50-fold in strains carrying a gcr1 null mutation. cis-acting sequences that are sufficient for GCR1-dependent regulation of ENO2 expression were identified by using an enhancerless CYC1 promoter which is not normally dependent on GCR1 for expression. A 60-bp ENO2 sequence that was sufficient to provide high-level, GCR1-dependent transcriptional activation of the CYC1 promoter was identified. This 60-bp element could be subdivided into a 30-bp sequence containing a novel RAP1-binding site and a GCR1-binding site which did not activate CYC1 transcription and a 30-bp sequence containing a novel enhancer element that conferred moderate levels of GCR1-independent transcriptional activation. The 60-bp CGCR1-dependent upstream activator sequence is located immediately downstream from previously mapped overlapping binding sites for the regulatory proteins ABFI and RAP1. Evidence is presented that the overlapping ABFI- and RAP1-binding sites function together with sequences that bind GCR1 and RAP1 to stage transcriptional activation of ENO2 expression.

scholarly journals Neuropathy-Associated Egr2 Mutants Disrupt Cooperative Activation of Myelin Protein Zero by Egr2 and Sox10

2007 ◽  
Vol 27 (9) ◽  
pp. 3521-3529 ◽  
Author(s):  
Scott E. LeBlanc ◽  
Rebecca M. Ward ◽  
John Svaren
Keyword(s):  
Binding Sites ◽  
Myelin Protein ◽  
Myelin Protein Zero ◽  
Early Growth Response ◽  
Expression Of Genes ◽  
Myelin Associated Glycoprotein ◽  
Responsive Element ◽  
Protein Zero ◽  
Cooperative Activation

ABSTRACT Dominant mutations in the early growth response 2 (Egr2/Krox20) transactivator, a critical regulator of peripheral myelin development, have been associated with peripheral myelinopathies. These dominant mutants interfere with the expression of genes required for myelination by Schwann cells, including that for the most abundant peripheral myelin protein, Myelin protein zero (Mpz). In this study, we show that Egr2 mutants specifically affect an Egr2-responsive element within the Mpz first intron that also contains binding sites for the transcription factor Sox10. Furthermore, Egr2 activation through this element is impaired by mutation of the Sox10 binding sites. Using chromatin immunoprecipitation assays, we found that Egr2 and Sox10 bind to this element in myelinating sciatic nerve and that a dominant Egr2 mutant does not perturb Egr2 binding but rather attenuates binding of Sox10 to the Mpz intron element. Sox10 binding at other sites of Egr2/Sox10 synergy, including a novel site in the Myelin-associated glycoprotein (Mag) gene, is also reduced by the dominant Egr2 mutant. These results provide the first demonstration of binding of Egr2/Sox10 to adjacent sites in vivo and also demonstrate that neuropathy-associated Egr2 mutants antagonize binding of Sox10 at specific sites, thereby disrupting genetic control of the myelination program.

scholarly journals Sequences Just Upstream of the Simian Immunodeficiency Virus Core Enhancer Allow Efficient Replication in the Absence of NF-κB and Sp1 Binding Elements

1998 ◽  
Vol 72 (7) ◽  
pp. 5589-5598 ◽  
Author(s):  
Stefan Pöhlmann ◽  
Stefan Flöss ◽  
Petr O. Ilyinskii ◽  
Thomas Stamminger ◽  
Frank Kirchhoff
Keyword(s):  
Viral Replication ◽  
Binding Site ◽  
Simian Immunodeficiency Virus ◽  
Binding Sites ◽  
Regulatory Element ◽  
Virus Production ◽  
Enhancer Element ◽  
Immunodeficiency Virus ◽  
Efficient Replication

ABSTRACT Large deletions of the upstream U3 sequences in the long terminal repeats (LTRs) of human immunodeficiency virus and simian immunodeficiency virus (SIV) accumulate in vivo in the absence of an intact nef gene. In the SIV U3 region, about 65 bp just upstream of the single NF-κB binding site always remained intact, and some evidence for a novel enhancer element in this region exists. We analyzed the transcriptional and replicative capacities of SIVmac239 mutants containing deletions or mutations in these upstream U3 sequences and/or the NF-κB and Sp1 binding sites. Even in the absence of 400 bp of upstream U3 sequences, the NF-κB site and all four Sp1 binding sites, the SIV promoter maintained about 15% of the wild-type LTR activity and was fully responsive to Tat activation in transient reporter assays. The effects of these deletions on virus production after transfection of COS-1 cells with full-length proviral constructs were much greater. Deletion of the upstream U3 sequences had no significant influence on viral replication when either the single NF-κB site or the Sp1 binding sites were intact. In contrast, the 26 bp of sequence located immediately upstream of the NF-κB site was essential for efficient replication when all core enhancer elements were deleted. A purine-rich site in this region binds specifically to the transcription factor Elf-1, a member of the etsproto-oncogene-encoded family. Our results indicate a high degree of functional redundancy in the SIVmac U3 region. Furthermore, we defined a novel regulatory element located immediately upstream of the NF-κB binding site that allows efficient viral replication in the absence of the entire core enhancer region.

scholarly journals Genes encoding components of the olfactory signal transduction cascade contain a DNA binding site that may direct neuronal expression.

1993 ◽  
Vol 13 (9) ◽  
pp. 5805-5813 ◽  
Author(s):  
M M Wang ◽  
R Y Tsai ◽  
K A Schrader ◽  
R R Reed
Keyword(s):  
Signal Transduction ◽  
Dna Binding ◽  
Binding Site ◽  
Binding Sites ◽  
Consensus Sequence ◽  
Initiation Site ◽  
Olfactory Neuron ◽  
Promoter Regions ◽  
Transcriptional Initiation ◽  
Genes Encoding

Genes which mediate odorant signal transduction are expressed at high levels in neurons of the olfactory epithelium. The molecular mechanism governing the restricted expression of these genes likely involves tissue-specific DNA binding proteins which coordinately activate transcription through sequence-specific interactions with olfactory promoter regions. We have identified binding sites for the olfactory neuron-specific transcription factor, Olf-1, in the sequences surrounding the transcriptional initiation site of five olfactory neuron-specific genes. The Olf-1 binding sites described define the consensus sequence YTCCCYRGGGAR. In addition, we have identified a second binding site, the U site, in the olfactory cyclic nucleotide gated channel and type III cyclase promoters, which binds factors present in all tissue examined. These experiments support a model in which expression of Olf-1 in the sensory neurons coordinately activates a set of olfactory neuron-specific genes. Furthermore, expression of a subset of these genes may be modulated by additional binding factors.

scholarly journals Transcriptional Regulation of Genes Encoding the Selenium-Free [NiFe]-Hydrogenases in the Archaeon Methanococcus voltae Involves Positive and Negative Control Elements

Genetics ◽  
1999 ◽  
Vol 152 (4) ◽  
pp. 1335-1341
Author(s):  
Izabela Noll ◽  
Steffen Müller ◽  
Albrecht Klein
Keyword(s):  
Intergenic Region ◽  
Genetic Information ◽  
Regulatory Element ◽  
Transcription Unit ◽  
Negative Control ◽  
Negative Regulation ◽  
Negative Regulatory Element ◽  
Methanococcus Voltae ◽  
Genes Encoding ◽  
Made In

Abstract Methanococcus voltae harbors genetic information for two pairs of homologous [NiFe]-hydrogenases. Two of the enzymes contain selenocysteine, while the other two gene groups encode apparent isoenzymes that carry cysteinyl residues in the homologous positions. The genes coding for the selenium-free enzymes, frc and vhc, are expressed only under selenium limitation. They are transcribed out of a common intergenic region. A series of deletions made in the intergenic region localized a common negative regulatory element for the vhc and frc promoters as well as two activator elements that are specific for each of the two transcription units. Repeated sequences, partially overlapping the frc promoter, were also detected. Mutations in these repeated heptanucleotide sequences led to a weak induction of a reporter gene under the control of the frc promoters in the presence of selenium. This result suggests that the heptamer repeats contribute to the negative regulation of the frc transcription unit.

scholarly journals Multi-omic profiling of pituitary thyrotropic cells and progenitors

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Alexandre Z. Daly ◽  
Lindsey A. Dudley ◽  
Michael T. Peel ◽  
Stephen A. Liebhaber ◽  
Stephen C. J. Parker ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Pituitary Gland ◽  
Cell Lines ◽  
Binding Sites ◽  
Critical Factor ◽  
Regulatory Elements ◽  
Thyroid Stimulating Hormone ◽  
Neuroendocrine Cells ◽  
Bzip Transcription Factor ◽  
Enhancer Element

Abstract Background The pituitary gland is a neuroendocrine organ containing diverse cell types specialized in secreting hormones that regulate physiology. Pituitary thyrotropes produce thyroid-stimulating hormone (TSH), a critical factor for growth and maintenance of metabolism. The transcription factors POU1F1 and GATA2 have been implicated in thyrotrope fate, but the transcriptomic and epigenomic landscapes of these neuroendocrine cells have not been characterized. The goal of this work was to discover transcriptional regulatory elements that drive thyrotrope fate. Results We identified the transcription factors and epigenomic changes in chromatin that are associated with differentiation of POU1F1-expressing progenitors into thyrotropes using cell lines that represent an undifferentiated Pou1f1 lineage progenitor (GHF-T1) and a committed thyrotrope line that produces TSH (TαT1). We compared RNA-seq, ATAC-seq, histone modification (H3K27Ac, H3K4Me1, and H3K27Me3), and POU1F1 binding in these cell lines. POU1F1 binding sites are commonly associated with bZIP transcription factor consensus binding sites in GHF-T1 cells and Helix-Turn-Helix (HTH) or basic Helix-Loop-Helix (bHLH) factors in TαT1 cells, suggesting that these classes of transcription factors may recruit or cooperate with POU1F1 binding at unique sites. We validated enhancer function of novel elements we mapped near Cga, Pitx1, Gata2, and Tshb by transfection in TαT1 cells. Finally, we confirmed that an enhancer element near Tshb can drive expression in thyrotropes of transgenic mice, and we demonstrate that GATA2 enhances Tshb expression through this element. Conclusion These results extend the ENCODE multi-omic profiling approach to the pituitary gland, which should be valuable for understanding pituitary development and disease pathogenesis. Graphical abstract

scholarly journals The Basic Helix-Loop-Helix Transcription Factor Cph2 Regulates Hyphal Development in CandidaalbicansPartly via Tec1

2001 ◽  
Vol 21 (19) ◽  
pp. 6418-6428 ◽  
Author(s):  
Shelley Lane ◽  
Song Zhou ◽  
Ting Pan ◽  
Qian Dai ◽  
Haoping Liu
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Binding Sites ◽  
Regulatory Element ◽  
Ectopic Expression ◽  
Mitogen Activated Protein Kinase ◽  
Northern Analysis ◽  
Hyphal Development ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix

ABSTRACT Candida albicans undergoes a morphogenetic switch from budding yeast to hyphal growth form in response to a variety of stimuli and growth conditions. Multiple signaling pathways, including a Cph1-mediated mitogen-activated protein kinase pathway and an Efg1-mediated cyclic AMP/protein kinase A pathway, regulate the transition. Here we report the identification of a basic helix-loop-helix transcription factor of the Myc subfamily (Cph2) by its ability to promote pseudohyphal growth inSaccharomyces cerevisiae. Like sterol response element binding protein 1, Cph2 has a Tyr instead of a conserved Arg in the basic DNA binding region. Cph2 regulates hyphal development in C. albicans, ascph2/cph2 mutant strains show medium-specific impairment in hyphal development and in the induction of hypha-specific genes. However, many hypha-specific genes do not have potential Cph2 binding sites in their upstream regions. Interestingly, upstream sequences of all known hypha-specific genes are found to contain potential binding sites for Tec1, a regulator of hyphal development. Northern analysis shows that TEC1 transcription is highest in the medium in which cph2/cph2 displays a defect in hyphal development, and Cph2 is necessary for this transcriptional induction of TEC1. In vitro gel mobility shift experiments show that Cph2 directly binds to the two sterol regulatory element 1-like elements upstream of TEC1. Furthermore, the ectopic expression of TEC1 suppresses the defect ofcph2/cph2 in hyphal development. Therefore, the function of Cph2 in hyphal transcription is mediated, in part, through Tec1. We further show that this function of Cph2 is independent of the Cph1- and Efg1-mediated pathways.

scholarly journals The transcriptional tissue specificity of the human proα1(I) collagen gene is determined by a negative cis-regulatory element in the promoter

1992 ◽  
Vol 286 (1) ◽  
pp. 179-185 ◽  
Author(s):  
C P Simkevich ◽  
J P Thompson ◽  
H Poppleton ◽  
R Raghow
Keyword(s):  
Tissue Specificity ◽  
Regulatory Element ◽  
Mesenchymal Cell ◽  
Cell Types ◽  
Regulatory Elements ◽  
Negative Influence ◽  
Collagen Gene ◽  
Specific Expression ◽  
Cis Acting ◽  
First Intron

The transcriptional activity of plasmid pCOL-KT, in which human pro alpha 1 (I) collagen gene upstream sequences up to -804 and most of the first intron (+474 to +1440) drive expression of the chloramphenicol acetyltransferase (CAT) gene [Thompson, Simkevich, Holness, Kang & Raghow (1991) J. Biol. Chem. 266, 2549-2556], was tested in a number of mesenchymal and non-mesenchymal cells. We observed that pCOL-KT was readily expressed in fibroblasts of human (IMR-90 and HFL-1), murine (NIH 3T3) and avian (SL-29) origin and in a human rhabdomyosarcoma cell line (A204), but failed to be expressed in human erythroleukaemia (K562) and rat pheochromocytoma (PC12) cells, indicating that the regulatory elements required for appropriate tissue-specific expression of the human pro alpha 1 (I) collagen gene were present in pCOL-KT. To delineate the nature of cis-acting sequences which determine the tissue specificity of pro alpha 1 (I) collagen gene expression, functional consequences of deletions in the promoter and first intron of pCOL-KT were tested in various cell types by transient expression assays. Cis elements in the promoter-proximal and intronic sequences displayed either a positive or a negative influence depending on the cell type. Thus deletion of fragments using EcoRV (nt -625 to -442 deleted), XbaI (-804 to -331) or SstII (+670 to +1440) resulted in 2-10-fold decreased expression in A204 and HFL-1 cells. The negative influences of deletions in the promoter-proximal sequences was apparently considerably relieved by deleting sequences in the first intron, and the constructs containing the EcoRV/SstII or XbaI/SstII double deletions were expressed to a much greater extent than either of the single deletion constructs. In contrast, the XbaI* deletion (nt -804 to -609), either alone or in combination with the intronic deletion, resulted in very high expression in all cells regardless of their collagen phenotype; the XbaI*/(-SstII) construct, which contained the intronic SstII fragment (+670 to +1440) in the reverse orientation, was not expressed in either mesenchymal or nonmesenchymal cells. Based on these results, we conclude that orientation-dependent interactions between negatively acting 5′-upstream sequences and the first intron determine the mesenchymal cell specificity of human pro alpha 1 (I) collagen gene transcription.

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