The Experts below are selected from a list of 86193 Experts worldwide ranked by ideXlab platform
Jason D. Lieb - One of the best experts on this subject based on the ideXlab platform.
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gene model 129 gm129 encodes a novel transcriptional repressor that modulates circadian gene expression
Journal of Biological Chemistry, 2014Co-Authors: Yunus Annayev, Sheera Adar, Yi Ying Chiou, Aziz Sancar, Jason D. Lieb, Rui YeAbstract:The mammalian circadian clock is a molecular oscillator composed of a feedback loop that involves transcriptional activators CLOCK and BMAL1, and repressors Cryptochrome (CRY) and Period (PER). Here we show that a direct CLOCK·BMAL1 target gene, Gm129, is a novel regulator of the feedback loop. ChIP analysis revealed that the CLOCK·BMAL1·CRY1 complex strongly occupies the promoter region of Gm129. Both mRNA and Protein levels of GM129 exhibit high amplitude circadian oscillations in mouse liver, and Gm129 gene encodes a nuclear-localized Protein that directly interacts with BMAL1 and represses CLOCK·BMAL1 activity. In vitro and in vivo Protein-DNA Interaction results demonstrate that, like CRY1, GM129 functions as a repressor by binding to the CLOCK·BMAL1 complex on DNA. Although Gm129−/− or Cry1−/− Gm129−/− mice retain a robust circadian rhythm, the peaks of Nr1d1 and Dbp mRNAs in liver exhibit a significant phase delay compared with control. Our results suggest that, in addition to CRYs and PERs, the GM129 Protein contributes to the transcriptional feedback loop by modulating CLOCK·BMAL1 activity as a transcriptional repressor.
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gene model 129 gm129 encodes a novel transcriptional repressor that modulates circadian gene expression
Journal of Biological Chemistry, 2014Co-Authors: Yunus Annayev, Sheera Adar, Yi Ying Chiou, Aziz Sancar, Jason D. Lieb, Rui YeAbstract:The mammalian circadian clock is a molecular oscillator composed of a feedback loop that involves transcriptional activators CLOCK and BMAL1, and repressors Cryptochrome (CRY) and Period (PER). Here we show that a direct CLOCK·BMAL1 target gene, Gm129, is a novel regulator of the feedback loop. ChIP analysis revealed that the CLOCK·BMAL1·CRY1 complex strongly occupies the promoter region of Gm129. Both mRNA and Protein levels of GM129 exhibit high amplitude circadian oscillations in mouse liver, and Gm129 gene encodes a nuclear-localized Protein that directly interacts with BMAL1 and represses CLOCK·BMAL1 activity. In vitro and in vivo Protein-DNA Interaction results demonstrate that, like CRY1, GM129 functions as a repressor by binding to the CLOCK·BMAL1 complex on DNA. Although Gm129−/− or Cry1−/− Gm129−/− mice retain a robust circadian rhythm, the peaks of Nr1d1 and Dbp mRNAs in liver exhibit a significant phase delay compared with control. Our results suggest that, in addition to CRYs and PERs, the GM129 Protein contributes to the transcriptional feedback loop by modulating CLOCK·BMAL1 activity as a transcriptional repressor.
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ChIPOTle: a user-friendly tool for the analysis of ChIP-chip data
Genome Biology, 2005Co-Authors: Michael J Buck, Andrew B Nobel, Jason D. LiebAbstract:ChIPOTle (Chromatin ImmunoPrecipitation On Tiled arrays) takes advantage of two unique properties of ChIP-chip data: the single-tailed nature of the data, caused by specific enrichment but not specific depletion of genomic fragments; and the predictable enrichment of DNA fragments adjacent to sites of direct Protein-DNA Interaction. Implemented as a Microsoft Excel macro written in Visual Basic, ChIPOTle uses a sliding window approach that yields improvements in the identification of bona fide sites of Protein-DNA Interaction.
Rui Ye - One of the best experts on this subject based on the ideXlab platform.
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gene model 129 gm129 encodes a novel transcriptional repressor that modulates circadian gene expression
Journal of Biological Chemistry, 2014Co-Authors: Yunus Annayev, Sheera Adar, Yi Ying Chiou, Aziz Sancar, Jason D. Lieb, Rui YeAbstract:The mammalian circadian clock is a molecular oscillator composed of a feedback loop that involves transcriptional activators CLOCK and BMAL1, and repressors Cryptochrome (CRY) and Period (PER). Here we show that a direct CLOCK·BMAL1 target gene, Gm129, is a novel regulator of the feedback loop. ChIP analysis revealed that the CLOCK·BMAL1·CRY1 complex strongly occupies the promoter region of Gm129. Both mRNA and Protein levels of GM129 exhibit high amplitude circadian oscillations in mouse liver, and Gm129 gene encodes a nuclear-localized Protein that directly interacts with BMAL1 and represses CLOCK·BMAL1 activity. In vitro and in vivo Protein-DNA Interaction results demonstrate that, like CRY1, GM129 functions as a repressor by binding to the CLOCK·BMAL1 complex on DNA. Although Gm129−/− or Cry1−/− Gm129−/− mice retain a robust circadian rhythm, the peaks of Nr1d1 and Dbp mRNAs in liver exhibit a significant phase delay compared with control. Our results suggest that, in addition to CRYs and PERs, the GM129 Protein contributes to the transcriptional feedback loop by modulating CLOCK·BMAL1 activity as a transcriptional repressor.
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gene model 129 gm129 encodes a novel transcriptional repressor that modulates circadian gene expression
Journal of Biological Chemistry, 2014Co-Authors: Yunus Annayev, Sheera Adar, Yi Ying Chiou, Aziz Sancar, Jason D. Lieb, Rui YeAbstract:The mammalian circadian clock is a molecular oscillator composed of a feedback loop that involves transcriptional activators CLOCK and BMAL1, and repressors Cryptochrome (CRY) and Period (PER). Here we show that a direct CLOCK·BMAL1 target gene, Gm129, is a novel regulator of the feedback loop. ChIP analysis revealed that the CLOCK·BMAL1·CRY1 complex strongly occupies the promoter region of Gm129. Both mRNA and Protein levels of GM129 exhibit high amplitude circadian oscillations in mouse liver, and Gm129 gene encodes a nuclear-localized Protein that directly interacts with BMAL1 and represses CLOCK·BMAL1 activity. In vitro and in vivo Protein-DNA Interaction results demonstrate that, like CRY1, GM129 functions as a repressor by binding to the CLOCK·BMAL1 complex on DNA. Although Gm129−/− or Cry1−/− Gm129−/− mice retain a robust circadian rhythm, the peaks of Nr1d1 and Dbp mRNAs in liver exhibit a significant phase delay compared with control. Our results suggest that, in addition to CRYs and PERs, the GM129 Protein contributes to the transcriptional feedback loop by modulating CLOCK·BMAL1 activity as a transcriptional repressor.
Daniel Amadornoguez - One of the best experts on this subject based on the ideXlab platform.
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transcriptomic Protein DNA Interaction and metabolomic studies of vosa velb and weta in aspergillus nidulans asexual spores
Mbio, 2021Co-Authors: Matthew E. Mead, Ye-eun Son, Mi-kyung Lee, George F. Neuhaus, Donovon A. Adpressa, Julia Martien, Heungyun Moon, Daniel AmadornoguezAbstract:In filamentous fungi, asexual development involves cellular differentiation and metabolic remodeling leading to the formation of intact asexual spores. The development of asexual spores (conidia) in Aspergillus is precisely coordinated by multiple transcription factors (TFs), including VosA, VelB, and WetA. Notably, these three TFs are essential for the structural and metabolic integrity, i.e., proper maturation, of conidia in the model fungus Aspergillus nidulans To gain mechanistic insight into the complex regulatory and interdependent roles of these TFs in asexual sporogenesis, we carried out multi-omics studies on the transcriptome, Protein-DNA Interactions, and primary and secondary metabolism employing A. nidulans conidia. RNA sequencing and chromatin immunoprecipitation sequencing analyses have revealed that the three TFs directly or indirectly regulate the expression of genes associated with heterotrimeric G-Protein signal transduction, mitogen-activated Protein (MAP) kinases, spore wall formation and structural integrity, asexual development, and primary/secondary metabolism. In addition, metabolomics analyses of wild-type and individual mutant conidia indicate that these three TFs regulate a diverse array of primary metabolites, including those in the tricarboxylic acid (TCA) cycle, certain amino acids, and trehalose, and secondary metabolites such as sterigmatocystin, emericellamide, austinol, and dehydroaustinol. In summary, WetA, VosA, and VelB play interdependent, overlapping, and distinct roles in governing morphological development and primary/secondary metabolic remodeling in Aspergillus conidia, leading to the production of vital conidia suitable for fungal proliferation and dissemination.IMPORTANCE Filamentous fungi produce a vast number of asexual spores that act as efficient propagules. Due to their infectious and/or allergenic nature, fungal spores affect our daily life. Aspergillus species produce asexual spores called conidia; their formation involves morphological development and metabolic changes, and the associated regulatory systems are coordinated by multiple transcription factors (TFs). To understand the underlying global regulatory programs and cellular outcomes associated with conidium formation, genomic and metabolomic analyses were performed in the model fungus Aspergillus nidulans Our results show that the fungus-specific WetA/VosA/VelB TFs govern the coordination of morphological and chemical developments during sporogenesis. The results of this study provide insights into the interdependent, overlapping, or distinct genetic regulatory networks necessary to produce intact asexual spores. The findings are relevant for other Aspergillus species such as the major human pathogen Aspergillus fumigatus and the aflatoxin producer Aspergillus flavus.
Yunus Annayev - One of the best experts on this subject based on the ideXlab platform.
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gene model 129 gm129 encodes a novel transcriptional repressor that modulates circadian gene expression
Journal of Biological Chemistry, 2014Co-Authors: Yunus Annayev, Sheera Adar, Yi Ying Chiou, Aziz Sancar, Jason D. Lieb, Rui YeAbstract:The mammalian circadian clock is a molecular oscillator composed of a feedback loop that involves transcriptional activators CLOCK and BMAL1, and repressors Cryptochrome (CRY) and Period (PER). Here we show that a direct CLOCK·BMAL1 target gene, Gm129, is a novel regulator of the feedback loop. ChIP analysis revealed that the CLOCK·BMAL1·CRY1 complex strongly occupies the promoter region of Gm129. Both mRNA and Protein levels of GM129 exhibit high amplitude circadian oscillations in mouse liver, and Gm129 gene encodes a nuclear-localized Protein that directly interacts with BMAL1 and represses CLOCK·BMAL1 activity. In vitro and in vivo Protein-DNA Interaction results demonstrate that, like CRY1, GM129 functions as a repressor by binding to the CLOCK·BMAL1 complex on DNA. Although Gm129−/− or Cry1−/− Gm129−/− mice retain a robust circadian rhythm, the peaks of Nr1d1 and Dbp mRNAs in liver exhibit a significant phase delay compared with control. Our results suggest that, in addition to CRYs and PERs, the GM129 Protein contributes to the transcriptional feedback loop by modulating CLOCK·BMAL1 activity as a transcriptional repressor.
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gene model 129 gm129 encodes a novel transcriptional repressor that modulates circadian gene expression
Journal of Biological Chemistry, 2014Co-Authors: Yunus Annayev, Sheera Adar, Yi Ying Chiou, Aziz Sancar, Jason D. Lieb, Rui YeAbstract:The mammalian circadian clock is a molecular oscillator composed of a feedback loop that involves transcriptional activators CLOCK and BMAL1, and repressors Cryptochrome (CRY) and Period (PER). Here we show that a direct CLOCK·BMAL1 target gene, Gm129, is a novel regulator of the feedback loop. ChIP analysis revealed that the CLOCK·BMAL1·CRY1 complex strongly occupies the promoter region of Gm129. Both mRNA and Protein levels of GM129 exhibit high amplitude circadian oscillations in mouse liver, and Gm129 gene encodes a nuclear-localized Protein that directly interacts with BMAL1 and represses CLOCK·BMAL1 activity. In vitro and in vivo Protein-DNA Interaction results demonstrate that, like CRY1, GM129 functions as a repressor by binding to the CLOCK·BMAL1 complex on DNA. Although Gm129−/− or Cry1−/− Gm129−/− mice retain a robust circadian rhythm, the peaks of Nr1d1 and Dbp mRNAs in liver exhibit a significant phase delay compared with control. Our results suggest that, in addition to CRYs and PERs, the GM129 Protein contributes to the transcriptional feedback loop by modulating CLOCK·BMAL1 activity as a transcriptional repressor.
Kevin Struhl - One of the best experts on this subject based on the ideXlab platform.
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relationships between p63 binding DNA sequence transcription activity and biological function in human cells
Molecular Cell, 2006Co-Authors: Annie Yang, Zhou Zhu, Philipp Kapranov, Frank Mckeon, George M Church, Thomas R Gingeras, Kevin StruhlAbstract:Using tiled microarrays covering the entire human genome, we identify approximately 5800 target sites for p63, a p53 homolog essential for stratified epithelial development. p63 targets are enriched for genes involved in cell adhesion, proliferation, death, and signaling pathways. The quality of the derived DNA sequence motif for p63 targets correlates with binding strength binding in vivo, but only a small minority of motifs in the genome is bound by p63. Conversely, many p63 targets have motif scores expected for random genomic regions. Thus, p63 binding in vivo is highly selective and often requires additional factors beyond the simple Protein-DNA Interaction. There is a significant, but complex, relationship between p63 target sites and p63-responsive genes, with DeltaNp63 isoforms being linked to transcriptional activation. Many p63 binding regions are evolutionarily conserved and/or associated with sequence motifs for other transcription factors, suggesting that a substantial portion of p63 sites is biologically relevant.
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relationships between p63 binding DNA sequence transcription activity and biological function in human cells
Molecular Cell, 2006Co-Authors: Annie Yang, Philipp Kapranov, Frank Mckeon, George M Church, Thomas R Gingeras, Kevin StruhlAbstract:Summary Using tiled microarrays covering the entire human genome, we identify ∼5800 target sites for p63, a p53 homolog essential for stratified epithelial development. p63 targets are enriched for genes involved in cell adhesion, proliferation, death, and signaling pathways. The quality of the derived DNA sequence motif for p63 targets correlates with binding strength binding in vivo, but only a small minority of motifs in the genome is bound by p63. Conversely, many p63 targets have motif scores expected for random genomic regions. Thus, p63 binding in vivo is highly selective and often requires additional factors beyond the simple Protein-DNA Interaction. There is a significant, but complex, relationship between p63 target sites and p63-responsive genes, with ΔNp63 isoforms being linked to transcriptional activation. Many p63 binding regions are evolutionarily conserved and/or associated with sequence motifs for other transcription factors, suggesting that a substantial portion of p63 sites is biologically relevant.
