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 antagonizing or recruiting the de novo DNA methylation complex. In mouse oogenesis, DNA methylation establishment occurs on a largely unmethylated genome and in nondividing cells, making it a highly informative model for examining how histone modifications can shape the DNA methylome. Using a chromatin immunoprecipitation (ChIP) and genome-wide sequencing (ChIP-seq) protocol optimized for low cell numbers and novel techniques for isolating primary and growing oocytes, profiles were generated for histone modifications implicated in promoting or inhibiting DNA methylation. CGIs destined for DNA methylation show reduced protective H3K4 dimethylation (H3K4me2) and trimethylation (H3K4me3) in both primary and growing oocytes, while permissive H3K36me3 increases specifically at these CGIs in growing oocytes. Methylome profiling of oocytes deficient in H3K4 demethylase KDM1A or KDM1B indicated that removal of H3K4 methylation is necessary for proper methylation establishment at CGIs. This work represents the first systematic study performing ChIP-seq in oocytes and shows that histone remodeling in the mammalian oocyte helps direct de novo DNA methylation events.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Stewart KR,Veselovska L,Kim J,Huang J,Saadeh H,Tomizawa S,Smallwood SA,Chen T,Kelsey Gdoi
10.1101/gad.271353.115subject
Has Abstractpub_date
2015-12-01 00:00:00pages
2449-62issue
23eissn
0890-9369issn
1549-5477pii
gad.271353.115journal_volume
29pub_type
杂志文章abstract::RNAi has revolutionized reverse genetics; however, RNAi is not necessarily ubiquitous or constitutive. Lund and colleagues (pp. 1121-1131) show that microRNA (miRNA) effector Argonautes (Agos) are limiting and easily saturated during early Xenopus embryogenesis. Moreover, this stage is devoid of slicing capacity. Supp...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.2062911
更新日期:2011-06-01 00:00:00
abstract::The Bloom's syndrome gene (BLM) plays a pivotal role in the maintenance of genomic stability in somatic cells. It encodes a DNA helicase (BLM) of the RecQ family, but the exact function of BLM remains elusive. To study this question, we have cloned the BLM homolog of the frog Xenopus laevis (xBLM) and have raised anti...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.822400
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abstract::A novel 15-kDa protein, RbfA, has been identified by virtue of its ability to act as a high copy suppressor of a previously characterized dominant cold-sensitive mutation (C23U) in 16S rRNA. RbfA is found associated with free 30S ribosomal subunits, but not with 70S ribosomes or polysomes, and is essential for maximal...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.5.626
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abstract::The v-erbA oncogene of avian erythroblastosis virus (AEV) encodes a ligand-independent mutated version of the chicken c-erbA alpha-encoded thyroid hormone receptor. The v-erbA gene product, a 75-kD gag/v-erbA fusion protein, is phosphorylated on Ser-16/17 of its v-erbA-encoded domain, and phosphorylation at this site ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.10.1663
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abstract::Cellular morphology is an essential determinant of cellular function in all kingdoms of life, yet little is known about how cell shape is controlled. Here we describe a molecular program that controls the early morphology of neurons through a metazoan-specific zinc finger protein, Unkempt. Depletion of Unkempt in mous...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.258483.115
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abstract::Tuberous sclerosis (TSC) is an autosomal dominant disease characterized by hamartoma formation in various organs and is caused by mutations targeting either the TSC1 or TSC2 genes. TSC1 and TSC2 proteins form a functionally interdependent dimeric complex. Phosphorylation of either TSC subunit by different kinases regu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1624008
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abstract::The liver is a unique organ with a remarkably high potential to regenerate upon injuries. In severely damaged livers where hepatocyte proliferation is impaired, facultative liver progenitor cells (LPCs) proliferate and are assumed to contribute to regeneration. An expansion of LPCs is often observed in patients with v...
journal_title:Genes & development
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abstract::The p53 tumor suppressor protein is the most well studied as a regulator of transcription in the nucleus, where it exists primarily as a tetramer. However, there are other oligomeric states of p53 that are relevant to its regulation and activities. In unstressed cells, p53 is normally held in check by MDM2 that target...
journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2018-03-01 00:00:00
abstract::Jun and Fos oncoproteins form a complex that regulates transcription from promoters containing AP-1 binding sites. The 'leucine zipper' domain of both Fos and Jun is necessary for the formation of the heterodimer, but the role of specific leucine residues is unclear. We have used site-specific mutagenesis to examine t...
journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
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abstract::PIWI clade Argonaute proteins silence transposon expression in animal gonads. Their target specificity is defined by bound ∼23- to 30-nucleotide (nt) PIWI-interacting RNAs (piRNAs) that are processed from single-stranded precursor transcripts via two distinct pathways. Primary piRNAs are defined by the endonuclease Zu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.267252.115
更新日期:2015-08-15 00:00:00
abstract::In the absence of growth signals, cells exit the cell cycle and enter into G0 or quiescence. Alternatively, cells enter senescence in response to inappropriate growth signals such as oncogene expression. The molecular mechanisms required for cell cycle exit into quiescence or senescence are poorly understood. The DREA...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2034211
更新日期:2011-04-15 00:00:00
abstract::Caenorhabditis elegans let-7, a founding member of the microRNA family, is predicted to bind to six sites in the 3'UTR of the mRNA of its target gene, lin-41, to down-regulate LIN-41. Here, we demonstrate that wild-type let-7 microRNA binds in vitro to RNA from the lin-41 3'UTR. This interaction is dependent on two co...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1165404
更新日期:2004-01-15 00:00:00
abstract::In this issue of Genes & Development, Dowen and colleagues (pp. 1515-1528) elegantly unify two previously unconnected aspects of physiology. The investigators provide significant genetic evidence to support a critical link between developmental timing decisions and the regulation of lipid mobilization at the transitio...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.285460.116
更新日期:2016-07-01 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::Signals from TGF-beta superfamily receptors are transduced to the nucleus by Smad proteins, which transcriptionally activate target genes. In Caenorhabditis elegans, defects in a TGF-beta-related pathway cause a reversible developmental arrest and metabolic shift at the dauer larval stage. Null mutations in daf-3 supp...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.20.2679
更新日期:1997-10-15 00:00:00
abstract::Constitutive activation of the Wnt/APC/beta-catenin pathway is a frequent initiating event in gastrointestinal carcinogenesis. Mutations in the Adenomatous Polyposis Coli (APC) gene up-regulate Wnt signaling by stabilizing beta-catenin and causing activation of targets important in proliferation control. Here we show ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1260605
更新日期:2005-02-01 00:00:00
abstract::In budding yeast, a switch between the mutually exclusive pathways of cell cycle progression and conjugation is controlled at Start in late G1 phase. Mating pheromones promote conjugation by arresting cells in G1 phase before Start. Pheromone-induced cell cycle arrest requires a functional FAR1 gene. We have found tha...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.5.833
更新日期:1993-05-01 00:00:00
abstract::The senescence-associated secretory phenotype (SASP) is a major trait of senescent cells, but the molecular regulators of SASP factor secretion are poorly understood. Mass spectrometry analysis revealed that secretory carrier membrane protein 4 (SCAMP4) levels were strikingly elevated on the surface of senescent cells...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.313270.118
更新日期:2018-07-01 00:00:00
abstract::RBP is a cellular protein that functions as a transcriptional repressor in mammalian cells. RBP has elicited great interest lately because of its established roles in regulating gene expression, in Drosophila and mouse development, and as a component of the Notch signal transduction pathway. This report focuses on the...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.11.1621
更新日期:1998-06-01 00:00:00
abstract::cappuccino and spire are unique Drosophila maternal-effect loci that participate in pattern formation in both the anteroposterior and dorsoventral axes of the early embryo. Mutant females produce embryos lacking pole cells, polar granules, and normal abdominal segmentation. They share these defects with the posterior ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.9.1437
更新日期:1989-09-01 00:00:00
abstract::Disruptions in the use of skeletal muscle lead to muscle atrophy. After short periods of disuse, muscle atrophy is reversible, and even after prolonged periods of inactivity, myofiber degeneration is uncommon. The pathways that regulate atrophy, initiated either by peripheral nerve damage, immobilization, aging, catab...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1318305
更新日期:2005-07-15 00:00:00
abstract::The amino-terminal histone tails are subject to covalent post-translational modifications such as acetylation, methylation, and phosphorylation. In the histone code hypothesis, these exposed and unstructured histone tails are accessible to a repertoire of regulatory factors that specifically recognize the various modi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1001502
更新日期:2002-06-15 00:00:00
abstract::Dorsal mesoderm induction in arthropods and ventral mesoderm induction in vertebrates are closely related processes that involve signals of the BMP family. In Drosophila, induction of visceral mesoderm, dorsal muscles, and the heart by Dpp is, at least in part, effected through the transcriptional activation and funct...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.15.2354
更新日期:1998-08-01 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::Identifying modifiers of dosage-sensitive genes involved in neurodegenerative disorders is imperative to discover novel genetic risk factors and potential therapeutic entry points. In this study, we focus on Ataxin-1 (ATXN1), a dosage-sensitive gene involved in the neurodegenerative disease spinocerebellar ataxia type...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.339317.120
更新日期:2020-09-01 00:00:00
abstract::During Drosophila embryogenesis, ectodermal cells of the lateral epithelium stretch in a coordinated fashion to internalize the amnioserosa cells and close the embryo dorsally. This process, dorsal closure, requires two signaling pathways: the Drosophila Jun-amino-terminal kinase (DJNK) pathway and the Dpp pathway. We...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.13.1717
更新日期:1997-07-01 00:00:00
abstract::Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC-β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical p...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.302679.117
更新日期:2017-08-15 00:00:00
abstract::Checkpoint genes maintain genomic stability by arresting cells after DNA damage. Many of these genes also control cell cycle events in unperturbed cells. By conducting a screen for checkpoint genes in zebrafish, we found that dtl/cdt2 is an essential component of the early, radiation-induced G2/M checkpoint. We subseq...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1482106
更新日期:2006-11-15 00:00:00
abstract::The basic helix-loop-helix (bHLH) gene Hes7, a putative Notch effector, encodes a transcriptional repressor. Here, we found that Hes7 expression oscillates in 2-h cycles in the presomitic mesoderm (PSM). In Hes7-null mice, somites are not properly segmented and their anterior-posterior polarity is disrupted. As a resu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.930601
更新日期:2001-10-15 00:00:00