Abstract:
:Oxidative tissues such as heart undergo a dramatic perinatal mitochondrial biogenesis to meet the high-energy demands after birth. PPARgamma coactivator-1 (PGC-1) alpha and beta have been implicated in the transcriptional control of cellular energy metabolism. Mice with combined deficiency of PGC-1alpha and PGC-1beta (PGC-1alphabeta(-/-) mice) were generated to investigate the convergence of their functions in vivo. The phenotype of PGC-1beta(-/-) mice was minimal under nonstressed conditions, including normal heart function, similar to that of PGC-1alpha(-/-) mice generated previously. In striking contrast to the singly deficient PGC-1 lines, PGC-1alphabeta(-/-) mice died shortly after birth with small hearts, bradycardia, intermittent heart block, and a markedly reduced cardiac output. Cardiac-specific ablation of the PGC-1beta gene on a PGC-1alpha-deficient background phenocopied the generalized PGC-1alphabeta(-/-) mice. The hearts of the PGC-1alphabeta(-/-) mice exhibited signatures of a maturational defect including reduced growth, a late fetal arrest in mitochondrial biogenesis, and persistence of a fetal pattern of gene expression. Brown adipose tissue (BAT) of PGC-1alphabeta(-/-) mice also exhibited a severe abnormality in function and mitochondrial density. We conclude that PGC-1alpha and PGC-1beta share roles that collectively are necessary for the postnatal metabolic and functional maturation of heart and BAT.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Lai L,Leone TC,Zechner C,Schaeffer PJ,Kelly SM,Flanagan DP,Medeiros DM,Kovacs A,Kelly DPdoi
10.1101/gad.1661708subject
Has Abstractpub_date
2008-07-15 00:00:00pages
1948-61issue
14eissn
0890-9369issn
1549-5477pii
22/14/1948journal_volume
22pub_type
杂志文章abstract::The distal enhancer of the T-cell receptor (TCR) alpha chain gene has become a paradigm for studies of the assembly and activity of architectural enhancer complexes. Here we have reconstituted regulated TCR alpha enhancer activity in vitro on chromatin templates using purified T-cell transcription factors (LEF-1, AML1...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.7.887
更新日期:1997-04-01 00:00:00
abstract::Gene inactivation can result when a delta element of the Ty1 transposon inserted into the yeast HIS4 promoter (his4-912delta) alters the transcription initiation site. Previous work has identified mutations that suppress this transcriptional defect by restoring the transcription start site to the native position, and ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.5.604
更新日期:1996-03-01 00:00:00
abstract::Previous studies have shown that differentiation of 3T3-L1 preadipocytes leads to the transcriptional activation of a group of adipose-specific genes. As an approach to defining the mechanism responsible for activating the expression of these genes, we investigated the binding of nuclear factors to the promoters of tw...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.9.1323
更新日期:1989-09-01 00:00:00
abstract::The lysosomal storage disorder galactosialidosis results from a primary deficiency of the protective protein/cathepsin A (PPCA), which in turn affects the activities of beta-galactosidase and neuraminidase. Mice homozygous for a null mutation at the PPCA locus present with signs of the disease shortly after birth and ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.21.2623
更新日期:1995-11-01 00:00:00
abstract::Although the human U2 and U6 snRNA genes are transcribed by different RNA polymerases (i.e., RNA polymerases II and III, respectively), their promoters are very similar in structure. Both contain a proximal sequence element (PSE) and an octamer motif-containing enhancer, and these elements are interchangeable between ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.8.1477
更新日期:1991-08-01 00:00:00
abstract::In yeast, galactose triggers a rapid GAL4-dependent induction of galactose/melibiose regulon (GAL/MEL) gene transcription, and glucose represses this activation. We discovered that alterations in the physical state of the GAL4 protein correlate with activation and repression of the GAL/MEL genes. Using Western immunob...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.8.1157
更新日期:1989-08-01 00:00:00
abstract::Intracellular heme levels must be tightly regulated to maintain proper mitochondrial respiration while minimizing toxicity, but the homeostatic mechanisms are not well understood. Here we report a novel negative feedback mechanism whereby the nuclear heme receptor Rev-erbalpha tightly controls the level of its own lig...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1825809
更新日期:2009-09-15 00:00:00
abstract::The yeast SAGA (Spt-Ada-Gcn5-acetyltransferase) coactivator complex exerts functions in gene expression, including activator interaction, histone acetylation, histone deubiquitination, mRNA export, chromatin recognition, and regulation of the basal transcription machinery. These diverse functions involve distinct modu...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.184705.111
更新日期:2012-03-15 00:00:00
abstract::The ubiquitin-specific protease (USP) family is the largest group of cysteine proteases. Cancer genomic analysis identified frequent amplification of USP21 (22%) in human pancreatic ductal adenocarcinoma (PDAC). USP21 overexpression correlates with human PDAC progression, and enforced expression of USP21 accelerates m...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.326314.119
更新日期:2019-10-01 00:00:00
abstract::Establishment of the steroid-producing Leydig cell lineage is an event downstream of Sry that is critical for masculinization of mammalian embryos. Neither the origin of fetal Leydig cell precursors nor the signaling pathway that specifies the Leydig cell lineage is known. Based on the sex-specific expression patterns...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.981202
更新日期:2002-06-01 00:00:00
abstract::The liver X receptors (LXRs) are members of the nuclear hormone receptor superfamily that are bound and activated by oxysterols. These receptors serve as sterol sensors to regulate the transcription of gene products that control intracellular cholesterol homeostasis through catabolism and transport. In this report, we...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.844900
更新日期:2000-11-15 00:00:00
abstract::The discovery of transcription factors (TFs) controlling pathways in health and disease is of paramount interest. We designed a widely applicable method, dubbed barcorded synthetic tandem repeat promoter screening (BC-STAR-PROM), to identify signal-activated TFs without any a priori knowledge about their properties. T...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.284828.116
更新日期:2016-08-15 00:00:00
abstract::The retinoblastoma tumor suppressor (pRb) protein associates with chromatin and regulates gene expression. Numerous studies have identified Rb-dependent RNA signatures, but the proteomic effects of Rb loss are largely unexplored. We acutely ablated Rb in adult mice and conducted a quantitative analysis of RNA and prot...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.264127.115
更新日期:2015-09-01 00:00:00
abstract::A complex array of genetic factors regulates neuronal dendrite morphology. Epigenetic regulation of gene expression represents a plausible mechanism to control pathways responsible for specific dendritic arbor shapes. By studying the Drosophila dendritic arborization (da) neurons, we discovered a role of the double-br...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.239962.114
更新日期:2014-09-01 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
abstract::rhomboid (rho) belongs to a group of four genes involved in the elaboration of positional information at a ventrolateral level in the Drosophila embryo. Mutations at any of these four loci also lead to a variety of other phenotypes, including reduction in the number of stretch receptor organs (chordotonal organs) in t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.2.190
更新日期:1990-02-01 00:00:00
abstract::TGF-β receptors phosphorylate SMAD2 and SMAD3 transcription factors, which then form heterotrimeric complexes with SMAD4 and cooperate with context-specific transcription factors to activate target genes. Here we provide biochemical and structural evidence showing that binding of SMAD2 to DNA depends on the conformati...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.330837.119
更新日期:2019-11-01 00:00:00
abstract::Sex determination is regulated by diverse pathways. Although upstream signals vary, a cysteine-rich DNA-binding domain (the DM motif) is conserved within downstream transcription factors of Drosophila melanogaster (Doublesex) and Caenorhabditis elegans (MAB-3). Vertebrate DM genes have likewise been identified and, re...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-07-15 00:00:00
abstract::Export to the cytoplasm of U3 RNA transcribed from a rat U3 gene injected into the nucleus of Xenopus oocytes indicates that the biogenesis of U3 RNA, like that of the previously studied Sm-precipitable nucleoplasmic snRNAs (U1, U2, U4, and U5), includes a cytoplasmic phase. The regulation of import of the U3 snRNA in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.6.1120
更新日期:1992-06-01 00:00:00
abstract::The Rbfox proteins (Rbfox1, Rbfox2, and Rbfox3) regulate the alternative splicing of many important neuronal transcripts and have been implicated in a variety of neurological disorders. However, their roles in brain development and function are not well understood, in part due to redundancy in their activities. Here w...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.182477.111
更新日期:2012-03-01 00:00:00
abstract::The E2F transcription factor is required for S phase in Drosophila. While it also triggers expression of replication genes at the G1-S transition, the relevance of this transcription is not clear because many of the induced gene products are sufficiently stable that new expression is not required for S phase. However,...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.12.1456
更新日期:1995-06-15 00:00:00
abstract::Alteration of nucleosomes by ATP-dependent remodeling complexes represents a critical step in the regulation of transcription. The human SWI/SNF (hSWI/SNF) family is composed of complexes that contain either Brg1 or hBrm as the central ATPase; however, these separate complexes have not been compared functionally. Here...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.872801
更新日期:2001-03-01 00:00:00
abstract::Ecsit is a cytosolic adaptor protein essential for inflammatory response and embryonic development via the Toll-like and BMP (bone morphogenetic protein) signal transduction pathways, respectively. Here, we demonstrate a mitochondrial function for Ecsit (an evolutionary conserved signaling intermediate in Toll pathway...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.408407
更新日期:2007-03-01 00:00:00
abstract::TDP-43 is a critical RNA-binding factor associated with pre-mRNA splicing in mammals. Its expression is tightly autoregulated, with loss of this regulation implicated in human neuropathology. We demonstrate that TDP-43 overexpression in humans and mice activates a 3' untranslated region (UTR) intron, resulting in exci...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.194829.112
更新日期:2012-08-01 00:00:00
abstract::Tissue morphogenesis during development is dependent on activities of the cadherin family of cell-cell adhesion proteins that includes classical cadherins, protocadherins, and atypical cadherins (Fat, Dachsous, and Flamingo). The extracellular domain of cadherins contains characteristic repeats that regulate homophili...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1486806
更新日期:2006-12-01 00:00:00
abstract::Genomic imprinting is an epigenetic process regulated by germline-derived DNA methylation, causing parental origin-specific monoallelic gene expression. Zinc finger protein 57 (ZFP57) is critical for maintenance of this epigenetic memory during post-fertilization reprogramming, yet incomplete penetrance of ZFP57 mutat...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.320069.118
更新日期:2019-01-01 00:00:00
abstract::X. laevis stage VI oocytes respond differently from unfertilized eggs when injected with the genes for X. laevis embryonic U1 RNAs, xU1b1, and xU1b2. Upon maturation of oocytes into eggs, the efficiency of transcription decreases greatly and the ratio of xU1b1 to xU1b2 RNA transcription changes. Moreover, DNA replicat...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.1.47
更新日期:1987-03-01 00:00:00
abstract::Direct reprogramming of fibroblasts to cardiomyocytes represents a potential means of restoring cardiac function following myocardial injury. AKT1 in the presence of four cardiogenic transcription factors, GATA4, HAND2, MEF2C, and TBX5 (AGHMT), efficiently induces the cardiac gene program in mouse embryonic fibroblast...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.305482.117
更新日期:2017-09-01 00:00:00
abstract::Expression of both N-myc and c-myc is induced rapidly and dramatically in normal pre-B cells after stimulation with interleukin-7 (IL-7), a pre-B cell-specific growth factor. These IL-7-induced increases in N-myc and c-myc expression are mediated at the transcriptional level; for N-myc, a major portion of the inductio...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.1.61
更新日期:1992-01-01 00:00:00
abstract::In recent years several new mouse models for lung cancer have been described. These include models for both non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Tumorigenesis in these conditional mouse tumor models can be initiated in adult mice through Cre-recombinase-induced activation of oncogenic ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1284505
更新日期:2005-03-15 00:00:00