LSH and G9a/GLP complex are required for developmentally programmed DNA methylation.

Abstract:

:LSH, a member of the SNF2 family of chromatin remodeling ATPases encoded by the Hells gene, is essential for normal levels of DNA methylation in the mammalian genome. While the role of LSH in the methylation of repetitive DNA sequences is well characterized, its contribution to the regulation of DNA methylation and the expression of protein-coding genes has not been studied in detail. In this report we investigate genome-wide patterns of DNA methylation at gene promoters in Hells(-/-) mouse embryonic fibroblasts (MEFs). We find that in the absence of LSH, DNA methylation is lost or significantly reduced at ∼20% of all normally methylated promoter sequences. As a consequence, a large number of genes are misexpressed in Hells(-/-) MEFs. Comparison of Hells(-/-) MEFs with wild-type MEFs and embryonic stem (ES) cells suggests that LSH is important for de novo DNA methylation events that accompany the establishment and differentiation of embryonic lineage cells. We further show that the generation of normal DNA methylation patterns and stable gene silencing at specific promoters require cooperation between LSH and the G9a/GLP complex of histone methylases. At such loci, G9a recruitment is compromised when LSH is absent or greatly reduced. Taken together, our data suggest a mechanism whereby LSH promotes binding of DNA methyltransferases and the G9a/GLP complex to specific loci and facilitates developmentally programmed DNA methylation and stable gene silencing during lineage commitment and differentiation.

journal_name

Genome Res

journal_title

Genome research

authors

Myant K,Termanis A,Sundaram AY,Boe T,Li C,Merusi C,Burrage J,de Las Heras JI,Stancheva I

doi

10.1101/gr.108498.110

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

83-94

issue

1

eissn

1088-9051

issn

1549-5469

pii

gr.108498.110

journal_volume

21

pub_type

杂志文章
  • Fusion of the human gene for the polyubiquitination coeffector UEV1 with Kua, a newly identified gene.

    abstract::UEV proteins are enzymatically inactive variants of the E2 ubiquitin-conjugating enzymes that regulate noncanonical elongation of ubiquitin chains. In Saccharomyces cerevisiae, UEV is part of the RAD6-mediated error-free DNA repair pathway. In mammalian cells, UEV proteins can modulate c-FOS transcription and the G2-M...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.gr-1405r

    authors: Thomson TM,Lozano JJ,Loukili N,Carrió R,Serras F,Cormand B,Valeri M,Díaz VM,Abril J,Burset M,Merino J,Macaya A,Corominas M,Guigó R

    更新日期:2000-11-01 00:00:00

  • Genome-reconstruction for eukaryotes from complex natural microbial communities.

    abstract::Microbial eukaryotes are integral components of natural microbial communities, and their inclusion is critical for many ecosystem studies, yet the majority of published metagenome analyses ignore eukaryotes. In order to include eukaryotes in environmental studies, we propose a method to recover eukaryotic genomes from...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.228429.117

    authors: West PT,Probst AJ,Grigoriev IV,Thomas BC,Banfield JF

    更新日期:2018-04-01 00:00:00

  • Estimating coarse gene network structure from large-scale gene perturbation data.

    abstract::Large scale gene perturbation experiments generate information about the number of genes whose activity is directly or indirectly affected by a gene perturbation. From this information, one can numerically estimate coarse structural network features such as the total number of direct regulatory interactions and the nu...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.193902

    authors: Wagner A

    更新日期:2002-02-01 00:00:00

  • Caenorhabditis elegans has scores of hedgehog-related genes: sequence and expression analysis.

    abstract::Previously, we have described novel families of genes, warthog (wrt) and groundhog (grd), in Caenorhabditis elegans. They are related to Hedgehog (Hh) through the carboxy-terminal autoprocessing domain (called Hog or Hint). A comprehensive survey revealed 10 genes with Hog/Hint modules in C. elegans. Five of these are...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.9.10.909

    authors: Aspöck G,Kagoshima H,Niklaus G,Bürglin TR

    更新日期:1999-10-01 00:00:00

  • A Plasmodium gene family encoding Maurer's cleft membrane proteins: structural properties and expression profiling.

    abstract::Upon invasion of the erythrocyte cell, the malaria parasite remodels its environment; in particular, it establishes a complex membrane network, which connects the parasitophorous vacuole to the host plasma membrane and is involved in protein transport and trafficking. We have identified a novel subtelomeric gene famil...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.2126104

    authors: Sam-Yellowe TY,Florens L,Johnson JR,Wang T,Drazba JA,Le Roch KG,Zhou Y,Batalov S,Carucci DJ,Winzeler EA,Yates JR 3rd

    更新日期:2004-06-01 00:00:00

  • Whole population, genome-wide mapping of hidden relatedness.

    abstract::We present GERMLINE, a robust algorithm for identifying segmental sharing indicative of recent common ancestry between pairs of individuals. Unlike methods with comparable objectives, GERMLINE scales linearly with the number of samples, enabling analysis of whole-genome data in large cohorts. Our approach is based on ...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.081398.108

    authors: Gusev A,Lowe JK,Stoffel M,Daly MJ,Altshuler D,Breslow JL,Friedman JM,Pe'er I

    更新日期:2009-02-01 00:00:00

  • Mutation detection using mass spectrometric separation of tiny oligonucleotide fragments.

    abstract::A DNA mutation detection protocol able to identify and characterize a previously unknown change in a given sequence in a rapid, efficient, sensitive, and inexpensive manner is required to take advantage of the resources now available to researchers through the genome sequencing projects. We have developed a method bas...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.gr-1578r

    authors: Elso C,Toohey B,Reid GE,Poetter K,Simpson RJ,Foote SJ

    更新日期:2002-09-01 00:00:00

  • Interaction between the X chromosome and an autosome regulates size sexual dimorphism in Portuguese Water Dogs.

    abstract::Size sexual dimorphism occurs in almost all mammals. In Portuguese Water Dogs, much of the difference in skeletal size between females and males is due to the interaction between a Quantitative Trait Locus (QTL) on the X-chromosome and a QTL linked to Insulin-like Growth Factor 1 (IGF-1) on the CFA 15 autosome. In fem...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.3712705

    authors: Chase K,Carrier DR,Adler FR,Ostrander EA,Lark KG

    更新日期:2005-12-01 00:00:00

  • Dynamic changes in replication timing and gene expression during lineage specification of human pluripotent stem cells.

    abstract::Duplication of the genome in mammalian cells occurs in a defined temporal order referred to as its replication-timing (RT) program. RT changes dynamically during development, regulated in units of 400-800 kb referred to as replication domains (RDs). Changes in RT are generally coordinated with transcriptional competen...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.187989.114

    authors: Rivera-Mulia JC,Buckley Q,Sasaki T,Zimmerman J,Didier RA,Nazor K,Loring JF,Lian Z,Weissman S,Robins AJ,Schulz TC,Menendez L,Kulik MJ,Dalton S,Gabr H,Kahveci T,Gilbert DM

    更新日期:2015-08-01 00:00:00

  • Comparative gene mapping: a fine-scale survey of chromosome rearrangements between ruminants and humans.

    abstract::A total of 202 genes were cytogenetically mapped to goat chromosomes, multiplying by five the total number of regional gene localizations in domestic ruminants (255). This map encompasses 249 and 173 common anchor loci regularly spaced along human and murine chromosomes, respectively, which makes it possible to perfor...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.8.9.901

    authors: Schibler L,Vaiman D,Oustry A,Giraud-Delville C,Cribiu EP

    更新日期:1998-09-01 00:00:00

  • Analysis of the floral transcriptome uncovers new regulators of organ determination and gene families related to flower organ differentiation in Gerbera hybrida (Asteraceae).

    abstract::Development of composite inflorescences in the plant family Asteraceae has features that cannot be studied in the traditional model plants for flower development. In Gerbera hybrida, inflorescences are composed of morphologically different types of flowers tightly packed into a flower head (capitulum). Individual flor...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.3043705

    authors: Laitinen RA,Immanen J,Auvinen P,Rudd S,Alatalo E,Paulin L,Ainasoja M,Kotilainen M,Koskela S,Teeri TH,Elomaa P

    更新日期:2005-04-01 00:00:00

  • Genome-wide parent-of-origin DNA methylation analysis reveals the intricacies of human imprinting and suggests a germline methylation-independent mechanism of establishment.

    abstract::Differential methylation between the two alleles of a gene has been observed in imprinted regions, where the methylation of one allele occurs on a parent-of-origin basis, the inactive X-chromosome in females, and at those loci whose methylation is driven by genetic variants. We have extensively characterized imprinted...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.164913.113

    authors: Court F,Tayama C,Romanelli V,Martin-Trujillo A,Iglesias-Platas I,Okamura K,Sugahara N,Simón C,Moore H,Harness JV,Keirstead H,Sanchez-Mut JV,Kaneki E,Lapunzina P,Soejima H,Wake N,Esteller M,Ogata T,Hata K,Nakabayashi

    更新日期:2014-04-01 00:00:00

  • Characterization of Alu repeats that are associated with trinucleotide and tetranucleotide repeat microsatellites.

    abstract::The association of subclasses of Alu repetitive elements with various classes of trinucleotide and tetranucleotide microsatellites was characterized as a first step toward advancing our understanding of the evolution of microsatellite repeats. In addition, information regarding the association of specific classes of m...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.7.7.716

    authors: Yandava CN,Gastier JM,Pulido JC,Brody T,Sheffield V,Murray J,Buetow K,Duyk GM

    更新日期:1997-07-01 00:00:00

  • The evolution of sex-biased gene expression in the Drosophila brain.

    abstract::Genes with sex-biased expression in Drosophila are thought to underlie sexually dimorphic phenotypes and have been shown to possess unique evolutionary properties. However, the forces and constraints governing the evolution of sex-biased genes in the somatic tissues of Drosophila are largely unknown. By using populati...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.259069.119

    authors: Khodursky S,Svetec N,Durkin SM,Zhao L

    更新日期:2020-06-01 00:00:00

  • New insulin-like proteins with atypical disulfide bond pattern characterized in Caenorhabditis elegans by comparative sequence analysis and homology modeling.

    abstract::We have identified three new families of insulin homologs in Caenorhabditis elegans. In two of these families, concerted mutations suggest that an additional disulfide bond links B and A domains, and that the A-domain internal disulfide bond is substituted by a hydrophobic interaction. Homology modeling remarkably con...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.8.4.348

    authors: Duret L,Guex N,Peitsch MC,Bairoch A

    更新日期:1998-04-01 00:00:00

  • The complete genome and proteome of Mycoplasma mobile.

    abstract::Although often considered "minimal" organisms, mycoplasmas show a wide range of diversity with respect to host environment, phenotypic traits, and pathogenicity. Here we report the complete genomic sequence and proteogenomic map for the piscine mycoplasma Mycoplasma mobile, noted for its robust gliding motility. For t...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.2674004

    authors: Jaffe JD,Stange-Thomann N,Smith C,DeCaprio D,Fisher S,Butler J,Calvo S,Elkins T,FitzGerald MG,Hafez N,Kodira CD,Major J,Wang S,Wilkinson J,Nicol R,Nusbaum C,Birren B,Berg HC,Church GM

    更新日期:2004-08-01 00:00:00

  • De novo rates and selection of large copy number variation.

    abstract::While copy number variation (CNV) is an active area of research, de novo mutation rates within human populations are not well characterized. By focusing on large (>100 kbp) events, we estimate the rate of de novo CNV formation in humans by analyzing 4394 transmissions from human pedigrees with and without neurocogniti...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.107680.110

    authors: Itsara A,Wu H,Smith JD,Nickerson DA,Romieu I,London SJ,Eichler EE

    更新日期:2010-11-01 00:00:00

  • Toward the development of a gene index to the human genome: an assessment of the nature of high-throughput EST sequence data.

    abstract::A rigorous analysis of the Merck-sponsored EST data with respect to known gene sequences increases the utility of the data set and helps refine methods for building a gene index. A highly curated human transcript data base was used as a reference data set of known genes. A detailed analysis of EST sequences derived fr...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.6.9.829

    authors: Aaronson JS,Eckman B,Blevins RA,Borkowski JA,Myerson J,Imran S,Elliston KO

    更新日期:1996-09-01 00:00:00

  • Whole-genome sequence assembly for mammalian genomes: Arachne 2.

    abstract::We previously described the whole-genome assembly program Arachne, presenting assemblies of simulated data for small to mid-sized genomes. Here we describe algorithmic adaptations to the program, allowing for assembly of mammalian-size genomes, and also improving the assembly of smaller genomes. Three principal change...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.828403

    authors: Jaffe DB,Butler J,Gnerre S,Mauceli E,Lindblad-Toh K,Mesirov JP,Zody MC,Lander ES

    更新日期:2003-01-01 00:00:00

  • Gene loss and movement in the maize genome.

    abstract::Maize (Zea mays L. ssp. mays), one of the most important agricultural crops in the world, originated by hybridization of two closely related progenitors. To investigate the fate of its genes after tetraploidization, we analyzed the sequence of five duplicated regions from different chromosomal locations. We also compa...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.2701104

    authors: Lai J,Ma J,Swigonová Z,Ramakrishna W,Linton E,Llaca V,Tanyolac B,Park YJ,Jeong OY,Bennetzen JL,Messing J

    更新日期:2004-10-01 00:00:00

  • Transcriptional alterations in glioma result primarily from DNA methylation-independent mechanisms.

    abstract::In cancer cells, aberrant DNA methylation is commonly associated with transcriptional alterations, including silencing of tumor suppressor genes. However, multiple epigenetic mechanisms, including polycomb repressive marks, contribute to gene deregulation in cancer. To dissect the relative contribution of DNA methylat...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.249219.119

    authors: Court F,Le Boiteux E,Fogli A,Müller-Barthélémy M,Vaurs-Barrière C,Chautard E,Pereira B,Biau J,Kemeny JL,Khalil T,Karayan-Tapon L,Verrelle P,Arnaud P

    更新日期:2019-10-01 00:00:00

  • Comparative genomics of the Archaea (Euryarchaeota): evolution of conserved protein families, the stable core, and the variable shell.

    abstract::Comparative analysis of the protein sequences encoded in the four euryarchaeal species whose genomes have been sequenced completely (Methanococcus jannaschii, Methanobacterium thermoautotrophicum, Archaeoglobus fulgidus, and Pyrococcus horikoshii) revealed 1326 orthologous sets, of which 543 are represented in all fou...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:

    authors: Makarova KS,Aravind L,Galperin MY,Grishin NV,Tatusov RL,Wolf YI,Koonin EV

    更新日期:1999-07-01 00:00:00

  • Multiple waves of recent DNA transposon activity in the bat, Myotis lucifugus.

    abstract::DNA transposons, or class 2 transposable elements, have successfully propagated in a wide variety of genomes. However, it is widely believed that DNA transposon activity has ceased in mammalian genomes for at least the last 40 million years. We recently reported evidence for the relatively recent activity of hAT and H...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.071886.107

    authors: Ray DA,Feschotte C,Pagan HJ,Smith JD,Pritham EJ,Arensburger P,Atkinson PW,Craig NL

    更新日期:2008-05-01 00:00:00

  • Spatial enhancer clustering and regulation of enhancer-proximal genes by cohesin.

    abstract::In addition to mediating sister chromatid cohesion during the cell cycle, the cohesin complex associates with CTCF and with active gene regulatory elements to form long-range interactions between its binding sites. Genome-wide chromosome conformation capture had shown that cohesin's main role in interphase genome orga...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.184986.114

    authors: Ing-Simmons E,Seitan VC,Faure AJ,Flicek P,Carroll T,Dekker J,Fisher AG,Lenhard B,Merkenschlager M

    更新日期:2015-04-01 00:00:00

  • The use of exome capture RNA-seq for highly degraded RNA with application to clinical cancer sequencing.

    abstract::RNA-seq by poly(A) selection is currently the most common protocol for whole transcriptome sequencing as it provides a broad, detailed, and accurate view of the RNA landscape. Unfortunately, the utility of poly(A) libraries is greatly limited when the input RNA is degraded, which is the norm for research tissues and c...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.189621.115

    authors: Cieslik M,Chugh R,Wu YM,Wu M,Brennan C,Lonigro R,Su F,Wang R,Siddiqui J,Mehra R,Cao X,Lucas D,Chinnaiyan AM,Robinson D

    更新日期:2015-09-01 00:00:00

  • Accurate typing of short tandem repeats from genome-wide sequencing data and its applications.

    abstract::Short tandem repeats (STRs) are implicated in dozens of human genetic diseases and contribute significantly to genome variation and instability. Yet profiling STRs from short-read sequencing data is challenging because of their high sequencing error rates. Here, we developed STR-FM, short tandem repeat profiling using...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.185892.114

    authors: Fungtammasan A,Ananda G,Hile SE,Su MS,Sun C,Harris R,Medvedev P,Eckert K,Makova KD

    更新日期:2015-05-01 00:00:00

  • Reconstructing large regions of an ancestral mammalian genome in silico.

    abstract::It is believed that most modern mammalian lineages arose from a series of rapid speciation events near the Cretaceous-Tertiary boundary. It is shown that such a phylogeny makes the common ancestral genome sequence an ideal target for reconstruction. Simulations suggest that with methods currently available, we can exp...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.2800104

    authors: Blanchette M,Green ED,Miller W,Haussler D

    更新日期:2004-12-01 00:00:00

  • A role for palindromic structures in the cis-region of maize Sirevirus LTRs in transposable element evolution and host epigenetic response.

    abstract::Transposable elements (TEs) proliferate within the genome of their host, which responds by silencing them epigenetically. Much is known about the mechanisms of silencing in plants, particularly the role of siRNAs in guiding DNA methylation. In contrast, little is known about siRNA targeting patterns along the length o...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.193763.115

    authors: Bousios A,Diez CM,Takuno S,Bystry V,Darzentas N,Gaut BS

    更新日期:2016-02-01 00:00:00

  • Pervasive polymorphic imprinted methylation in the human placenta.

    abstract::The maternal and paternal copies of the genome are both required for mammalian development, and this is primarily due to imprinted genes, those that are monoallelically expressed based on parent-of-origin. Typically, this pattern of expression is regulated by differentially methylated regions (DMRs) that are establish...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.196139.115

    authors: Hanna CW,Peñaherrera MS,Saadeh H,Andrews S,McFadden DE,Kelsey G,Robinson WP

    更新日期:2016-06-01 00:00:00

  • Integrative functional genomics identifies an enhancer looping to the SOX9 gene disrupted by the 17q24.3 prostate cancer risk locus.

    abstract::Genome-wide association studies (GWAS) are identifying genetic predisposition to various diseases. The 17q24.3 locus harbors the single nucleotide polymorphism (SNP) rs1859962 that is statistically associated with prostate cancer (PCa). It defines a 130-kb linkage disequilibrium (LD) block that lies in an ∼2-Mb gene d...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.135665.111

    authors: Zhang X,Cowper-Sal lari R,Bailey SD,Moore JH,Lupien M

    更新日期:2012-08-01 00:00:00