Abstract：
:The nuclear receptor Rev-erbα regulates circadian rhythm and metabolism, but its effects are modest and it has been considered to be a secondary regulator of the cell-autonomous clock. Here we report that depletion of Rev-erbα together with closely related Rev-erbβ has dramatic effects on the cell-autonomous clock as well as hepatic lipid metabolism. Mouse embryonic fibroblasts were rendered arrhythmic by depletion of both Rev-erbs. In mouse livers, Rev-erbβ mRNA and protein levels oscillate with a diurnal pattern similar to that of Rev-erbα, and both Rev-erbs are recruited to a remarkably similar set of binding sites across the genome, enriched near metabolic genes. Depletion of both Rev-erbs in liver synergistically derepresses several metabolic genes as well as genes that control the positive limb of the molecular clock. Moreover, deficiency of both Rev-erbs causes marked hepatic steatosis, in contrast to relatively subtle changes upon loss of either subtype alone. These findings establish the two Rev-erbs as major regulators of both clock function and metabolism, displaying a level of subtype collaboration that is unusual among nuclear receptors but common among core clock proteins, protecting the organism from major perturbations in circadian and metabolic physiology.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Bugge A,Feng D,Everett LJ,Briggs ER,Mullican SE,Wang F,Jager J,Lazar MAdoi
10.1101/gad.186858.112subject
Has Abstractpub_date
2012-04-01 00:00:00pages
657-67issue
7eissn
0890-9369issn
1549-5477pii
26/7/657journal_volume
26pub_type
杂志文章abstract：:The nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons (PTCs). Seven genes (smg-1-7, for suppressor with morphological effect on genitalia) that are essential for NMD were originally identified in the nematode Caenorhabditis elegans, and orthologs of these gene...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.417707
更新日期：2007-05-01 00:00:00
abstract：:Experiments in Xenopus have illustrated the importance of extracellular morphogens for embryonic gene regulation in vertebrates. Much less is known about how induction leads to the correct positioning of boundaries; for example, between germ layers. Here we report that the neuroectoderm/mesoderm boundary is controlled...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.409507
更新日期：2007-04-15 00:00:00
abstract：:Medulloblastomas are among the most common malignancies in childhood, and they are associated with substantial mortality and morbidity. The molecular pathogenesis as well as the ontogeny of these neoplasms is still poorly understood. We have generated a mouse model for medulloblastoma by Cre-LoxP-mediated inactivation...
journal_title：Genes & development
pub_type： 杂志文章
doi：
更新日期：2000-04-15 00:00:00
abstract：:Chromosomal translocations are a hallmark of hematopoietic malignancies. The initial molecular events or pathways that lead to translocations in hematopoietic cells are largely unknown, particularly in the stem cell-enriched population postulated to be the initial target for these events. We used in vitro differentiat...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1522807
更新日期：2007-05-01 00:00:00
abstract：:The release of Agrin by motoneurons activates the muscle-specific receptor tyrosine kinase (MuSK) as the main organizer of subsynaptic specializations at the neuromuscular junction. MuSK downstream signaling is largely undefined. Here we show that protein kinase CK2 interacts and colocalizes with MuSK at post-synaptic...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.375206
更新日期：2006-07-01 00:00:00
abstract：:To identify regions of the largest subunit of RNA polymerase that are potentially involved in transcript elongation and termination, we have characterized amino acid substitutions in the beta' subunit of Escherichia coli RNA polymerase that alter expression of reporter genes preceded by terminators in vivo. Terminatio...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.8.23.2913
更新日期：1994-12-01 00:00:00
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journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1165404
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journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.272237.115
更新日期：2016-03-01 00:00:00
abstract：:MicroRNAs (miRNAs) and transcription factors (TFs) are primary metazoan gene regulators. Whereas much attention has focused on finding the targets of both miRNAs and TFs, the transcriptional networks that regulate miRNA expression remain largely unexplored. Here, we present the first genome-scale Caenorhabditis elegan...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1678608
更新日期：2008-09-15 00:00:00
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journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.318675.118
更新日期：2018-12-01 00:00:00
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journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.7.7b.1364
更新日期：1993-07-01 00:00:00
abstract：:Ribosomal protein synthesis ceases upon maturation of Xenopus oocytes. We find that this cessation results from the dissociation of ribosomal protein mRNAs from polysomes and is accompanied by the deadenylation of these transcripts. A synthetic mRNA encoding ribosomal protein L1, microinjected into stage VI oocytes, i...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.2.5.598
更新日期：1988-05-01 00:00:00
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journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.210427.112
更新日期：2013-03-15 00:00:00
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journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.275107.115
更新日期：2016-02-01 00:00:00
abstract：:Unusually for a eukaryote, genes transcribed by RNA polymerase II (pol II) in Trypanosoma brucei are arranged in polycistronic transcription units. With one exception, no pol II promoter motifs have been identified, and how transcription is initiated remains an enigma. T. brucei has four histone variants: H2AZ, H2BV, ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1790409
更新日期：2009-05-01 00:00:00
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journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.3.12b.2025
更新日期：1989-12-01 00:00:00
abstract：:Hepatocyte nuclear factor 1 (HNF-1) is a transcriptional regulatory protein possibly involved in the activation of many liver-specifically expressed genes. HNF-1 mRNA is restricted to a small number of tissues, suggesting that the HNF-1 gene itself is regulated at the transcriptional level. We have isolated and charac...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.5.12a.2225
更新日期：1991-12-01 00:00:00
abstract：:The product of the nuclear MRS2 gene, Mrs2p, is the only candidate splicing factor essential for all group II introns in mitochondria of the yeast Saccharomyces cerevisiae. It has been shown to be an integral protein of the inner mitochondrial membrane, structurally and functionally related to the bacterial CorA Mg(2+...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.201301
更新日期：2001-09-01 00:00:00
abstract：:A cDNA library enriched for transcripts that accumulate from embryonic day 7 until day 1 posthatching was constructed from poly(A)+ RNA of chick optic lobe tissue. From this library, three recombinants were isolated that correspond to neural mRNAs appearing during the major period of synaptogenesis in the retinotectal...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1.7.699
更新日期：1987-09-01 00:00:00
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journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.7.4.546
更新日期：1993-04-01 00:00:00
abstract：:Erasure and subsequent reinstatement of DNA methylation in the germline, especially at imprinted CpG islands (CGIs), is crucial to embryogenesis in mammals. The mechanisms underlying DNA methylation establishment remain poorly understood, but a number of post-translational modifications of histones are implicated in a...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.271353.115
更新日期：2015-12-01 00:00:00
abstract：:Dendrite arborization patterns are critical determinants of neuronal function. To explore the basis of transcriptional regulation in dendrite pattern formation, we used RNA interference (RNAi) to screen 730 transcriptional regulators and identified 78 genes involved in patterning the stereotyped dendritic arbors of cl...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1391006
更新日期：2006-04-01 00:00:00
abstract：:The distal appendages (DAPs) of centrioles have been proposed to anchor cilia to the plasma membrane, but their molecular composition, assembly, and exact function in ciliogenesis remain poorly understood. Using quantitative centrosome proteomics and superresolution microscopy, we identified five DAP components, inclu...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.207043.112
更新日期：2013-01-15 00:00:00
abstract：:The alternatively spliced exon EIIIB is regulated in a cell type-specific manner in the rat fibronectin gene. Splicing of EIIIB into fibronectin mRNA is dependent on sequences in the intron immediately downstream of EIIIB. We show that a short, highly repeated TGCATG motif in this intron is important for cell type-spe...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.8.13.1561
更新日期：1994-07-01 00:00:00
abstract：:In the yeast Saccharomyces cerevisiae, sequence-specific DNA binding by the origin recognition complex (ORC) is responsible for selecting origins of DNA replication. In metazoans, origin selection is poorly understood and it is unknown whether specific DNA binding by metazoan ORC controls replication. To address this ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.13.20.2639
更新日期：1999-10-15 00:00:00
abstract：:The Drosophila external sensory organ forms in a lineage elaborating from a single precursor cell via a stereotypical series of asymmetric divisions. HAMLET transcription factor expression demarcates the lineage branch that generates two internal cell types, the external sensory neuron and thecogen. In HAMLET mutant o...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1170904
更新日期：2004-03-15 00:00:00
abstract：:The activity of the polyoma virus (PyV) origin of DNA replication was used as a sensitive assay for enhancer function in one- and two-cell mouse embryos by injecting embryos with plasmid DNA containing different PyV ori configurations, allowing them to continue development in vitro, and then measuring plasmid DNA repl...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.2.9.1115
更新日期：1988-09-01 00:00:00
abstract：:The Drosophila scratch (scrt) gene is expressed in most or all neuronal precursor cells and encodes a predicted zinc finger transcription factor closely related to the product of the mesoderm determination gene snail (sna). Adult flies homozygous for scrt null alleles have a reduced number of photoreceptors in the eye...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.9.19.2384
更新日期：1995-10-01 00:00:00
abstract：:Cell cycle transitions are often accompanied by the degradation of regulatory molecules. Targeting proteins to the proteasome for degradation is accomplished by the covalent addition of ubiquitin chains. The specificity of this pathway is largely dictated by a set of enzymes called ubiquitin ligases (or E3s). The anap...
journal_title：Genes & development
pub_type： 杂志文章,评审
doi：10.1101/gad.1478306
更新日期：2006-11-15 00:00:00
abstract：:Human lymphoblastoid cells derived from different healthy individuals display considerable variation in their transcription profiles. Here we show that such variation in gene expression underlies interindividual susceptibility to DNA damaging agents. The results demonstrate the massive differences in sensitivity acros...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1688508
更新日期：2008-10-01 00:00:00
