Swi6/HP1 recruits a JmjC domain protein to facilitate transcription of heterochromatic repeats.


:Heterochromatin formation is generally thought to result in transcriptional repression of target loci. However, RNAi-mediated heterochromatin assembly requires RNA polymerase II (Pol II) transcription. The mechanism facilitating Pol II accessibility to heterochromatin is unknown. We show that the fission yeast Epe1, a JmjC domain-containing protein and a negative regulator of heterochromatin, is distributed across all major heterochromatic domains and at certain meiotic genes. Remarkably, Epe1 is recruited to heterochromatic loci by the heterochromatin protein Swi6/HP1. Moreover, Epe1 acts in a heterochromatin-specific context to promote Pol II accessibility by counteracting repressive chromatin. This requires Epe1's JmjC domain, although the mechanism utilized might be distinct from other JmjC proteins that possess known demethylase activities. We also find that Epe1 is preferentially recruited to inverted repeats flanking centromeres to restrain the spread of pericentromeric heterochromatin. Our analyses suggest that Swi6/HP1 recruits opposing chromatin-modifying activities, the balancing of which is crucial for heterochromatin maintenance.


Mol Cell


Molecular cell


Zofall M,Grewal SI




Has Abstract


2006-06-09 00:00:00














  • PoxA, yjeK, and elongation factor P coordinately modulate virulence and drug resistance in Salmonella enterica.

    abstract::We report an interaction between poxA, encoding a paralog of lysyl tRNA-synthetase, and the closely linked yjeK gene, encoding a putative 2,3-beta-lysine aminomutase, that is critical for virulence and stress resistance in Salmonella enterica. Salmonella poxA and yjeK mutants share extensive phenotypic pleiotropy, inc...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Navarre WW,Zou SB,Roy H,Xie JL,Savchenko A,Singer A,Edvokimova E,Prost LR,Kumar R,Ibba M,Fang FC

    更新日期:2010-07-30 00:00:00

  • Rad54 functions as a heteroduplex DNA pump modulated by its DNA substrates and Rad51 during D loop formation.

    abstract::The displacement loop (D loop) is the product of homology search and DNA strand invasion, constituting a central intermediate in homologous recombination (HR). In eukaryotes, the Rad51 DNA strand exchange protein is assisted in D loop formation by the Rad54 motor protein. Curiously, Rad54 also disrupts D loops. How th...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Wright WD,Heyer WD

    更新日期:2014-02-06 00:00:00

  • PPAR gamma is required for placental, cardiac, and adipose tissue development.

    abstract::The nuclear hormone receptor PPAR gamma promotes adipogenesis and macrophage differentiation and is a primary pharmacological target in the treatment of type II diabetes. Here, we show that PPAR gamma gene knockout results in two independent lethal phases. Initially, PPAR gamma deficiency interferes with terminal diff...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Barak Y,Nelson MC,Ong ES,Jones YZ,Ruiz-Lozano P,Chien KR,Koder A,Evans RM

    更新日期:1999-10-01 00:00:00

  • Functional characterization of core promoter elements: DPE-specific transcription requires the protein kinase CK2 and the PC4 coactivator.

    abstract::Downstream core promoter elements are an expanding class of regulatory sequences that add considerable diversity to the promoter architecture of RNA polymerase II-transcribed genes. We set out to determine the factors necessary for downstream promoter element (DPE)-dependent transcription and find that, against expect...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Lewis BA,Sims RJ 3rd,Lane WS,Reinberg D

    更新日期:2005-05-13 00:00:00

  • Epigenetic instability due to defective replication of structured DNA.

    abstract::The accurate propagation of histone marks during chromosomal replication is proposed to rely on the tight coupling of replication with the recycling of parental histones to the daughter strands. Here, we show in the avian cell line DT40 that REV1, a key regulator of DNA translesion synthesis at the replication fork, i...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Sarkies P,Reams C,Simpson LJ,Sale JE

    更新日期:2010-12-10 00:00:00

  • Bursty gene expression in the intact mammalian liver.

    abstract::Bursts of nascent mRNA have been shown to lead to substantial cell-cell variation in unicellular organisms, facilitating diverse responses to environmental challenges. It is unknown whether similar bursts and gene-expression noise occur in mammalian tissues. To address this, we combine single molecule transcript count...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Bahar Halpern K,Tanami S,Landen S,Chapal M,Szlak L,Hutzler A,Nizhberg A,Itzkovitz S

    更新日期:2015-04-02 00:00:00

  • Advances in CLIP Technologies for Studies of Protein-RNA Interactions.

    abstract::RNA binding proteins (RBPs) regulate all aspects in the life cycle of RNA molecules. To elucidate the elements that guide RNA specificity, regulatory mechanisms, and functions of RBPs, methods that identify direct endogenous protein-RNA interactions are particularly valuable. UV crosslinking and immunoprecipitation (C...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审


    authors: Lee FCY,Ule J

    更新日期:2018-02-01 00:00:00

  • A Therapeutic Double Whammy: Transcriptional or Post-transcriptional Suppression of Microsatellite Repeat Toxicity by Cas9.

    abstract::Microsatellite expansion diseases are caused by unstable tandem repeats of 3-10 nucleotides that become pathogenic beyond a threshold number of copies. Two groups present different approaches to reduce pathogenesis by targeting deactivated Cas9 to either the DNA (Pinto et al., 2017) or the RNA (Batra et al., 2017) rep...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Rao AN,Cooper TA

    更新日期:2017-11-02 00:00:00

  • The orientation of mycobacteriophage Bxb1 integration is solely dependent on the central dinucleotide of attP and attB.

    abstract::Integration of the mycobacteriophage Bxb1 genome into its host chromosome is catalyzed by a serine-integrase, a member of the transposon-resolvase family of site-specific recombinases. These enzymes use a concerted mechanism of strand exchange involving double-stranded cleavages with two-base extensions, and covalent ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Ghosh P,Kim AI,Hatfull GF

    更新日期:2003-11-01 00:00:00

  • Heterochromatin formation in Drosophila is initiated through active removal of H3K4 methylation by the LSD1 homolog SU(VAR)3-3.

    abstract::Epigenetic indexing of chromatin domains by histone lysine methylation requires the balanced coordination of methyltransferase and demethylase activities. Here, we show that SU(VAR)3-3, the Drosophila homolog of the human LSD1 amine oxidase, demethylates H3K4me2 and H3K4me1 and facilitates subsequent H3K9 methylation ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Rudolph T,Yonezawa M,Lein S,Heidrich K,Kubicek S,Schäfer C,Phalke S,Walther M,Schmidt A,Jenuwein T,Reuter G

    更新日期:2007-04-13 00:00:00

  • A Reply to "MNase-Sensitive Complexes in Yeast: Nucleosomes and Non-histone Barriers," by Chereji et al.

    abstract::In this issue of Molecular Cell, Chereji et al. (2017) present new data on MNase-sensitive particles previously identified upstream of transcription start sites at many promoters in budding yeast, and they argue, based upon negative histone-ChIP results, that they are non-nucleosomal signals generated by transcription...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Kubik S,Bruzzone MJ,Albert B,Shore D

    更新日期:2017-02-02 00:00:00

  • Chromatin remodeling in vivo: evidence for a nucleosome sliding mechanism.

    abstract::Members of the ISWI family of chromatin remodeling factors exhibit ATP-dependent nucleosome sliding, loading, and spacing activities in vitro. However, it is unclear which of these activities are utilized by ISWI complexes to remodel chromatin in vivo. We therefore sought to identify the mechanisms of chromatin remode...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Fazzio TG,Tsukiyama T

    更新日期:2003-11-01 00:00:00

  • Insights into strand displacement and processivity from the crystal structure of the protein-primed DNA polymerase of bacteriophage phi29.

    abstract::The DNA polymerase from phage phi29 is a B family polymerase that initiates replication using a protein as a primer, attaching the first nucleotide of the phage genome to the hydroxyl of a specific serine of the priming protein. The crystal structure of phi29 DNA polymerase determined at 2.2 A resolution provides expl...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Kamtekar S,Berman AJ,Wang J,Lázaro JM,de Vega M,Blanco L,Salas M,Steitz TA

    更新日期:2004-11-19 00:00:00

  • Distinct autophagosomal-lysosomal fusion mechanism revealed by thapsigargin-induced autophagy arrest.

    abstract::Autophagy, a catabolic pathway that delivers cellular components to lysosomes for degradation, can be activated by stressful conditions such as nutrient starvation and endoplasmic reticulum (ER) stress. We report that thapsigargin, an ER stressor widely used to induce autophagy, in fact blocks autophagy. Thapsigargin ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Ganley IG,Wong PM,Gammoh N,Jiang X

    更新日期:2011-06-24 00:00:00

  • Hierarchical regulation of WASP/WAVE proteins.

    abstract::Members of the Wiskott-Aldrich syndrome protein (WASP) family control actin dynamics in eukaryotic cells by stimulating the actin nucleating activity of the Arp2/3 complex. The prevailing paradigm for WASP regulation invokes allosteric relief of autoinhibition by diverse upstream activators. Here we demonstrate an add...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Padrick SB,Cheng HC,Ismail AM,Panchal SC,Doolittle LK,Kim S,Skehan BM,Umetani J,Brautigam CA,Leong JM,Rosen MK

    更新日期:2008-11-07 00:00:00

  • CENP-A targeting moves a step back.

    abstract::In a recent issue of Molecular Cell, Pidoux et al. (2009) and Williams et al. (2009) identify S. pombe Scm3 as the proximate factor in the Cnp1/CENP-A deposition pathway, providing a direct connection to centromere-localized Mis16-Mis18. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Baker RE

    更新日期:2009-02-27 00:00:00

  • c-Jun downregulation by HDAC3-dependent transcriptional repression promotes osmotic stress-induced cell apoptosis.

    abstract::c-Jun, a major transcription factor in the activating protein 1 (AP-1) family of regulatory proteins, is activated by many physiologic and pathologic stimuli. However, whether c-jun is regulated by epigenetic modification of chromatin structure is not clear. We showed here that c-jun was transcriptionally repressed in...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Xia Y,Wang J,Liu TJ,Yung WK,Hunter T,Lu Z

    更新日期:2007-01-26 00:00:00

  • Structural Basis for the Modulation of Human KCNQ4 by Small-Molecule Drugs.

    abstract::Among the five KCNQ channels, also known as the Kv7 voltage-gated potassium (Kv) channels, KCNQ2-KCNQ5 control neuronal excitability. Dysfunctions of KCNQ2-KCNQ5 are associated with neurological disorders such as epilepsy, deafness, and neuropathic pain. Here, we report the cryoelectron microscopy (cryo-EM) structures...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Li T,Wu K,Yue Z,Wang Y,Zhang F,Shen H

    更新日期:2021-01-07 00:00:00

  • Conserved GU-rich elements mediate mRNA decay by binding to CUG-binding protein 1.

    abstract::We used computational algorithms to find conserved sequences in the 3' untranslated region (UTR) of transcripts that exhibited rapid decay in primary human T cells and found that the consensus sequence UGUUUGUUUGU, which we have termed a GU-rich element (GRE), was enriched in short-lived transcripts. Using a tet-off r...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Vlasova IA,Tahoe NM,Fan D,Larsson O,Rattenbacher B,Sternjohn JR,Vasdewani J,Karypis G,Reilly CS,Bitterman PB,Bohjanen PR

    更新日期:2008-02-01 00:00:00

  • A role for the deep orange and carnation eye color genes in lysosomal delivery in Drosophila.

    abstract::Deep orange and carnation are two of the classic eye color genes in Drosophila. Here, we demonstrate that Deep orange is part of a protein complex that localizes to endosomal compartments. A second component of this complex is Carnation, a homolog of Sec1p-like regulators of membrane fusion. Because complete loss of d...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Sevrioukov EA,He JP,Moghrabi N,Sunio A,Krämer H

    更新日期:1999-10-01 00:00:00

  • Mislocalized activation of oncogenic RTKs switches downstream signaling outcomes.

    abstract::Inappropriate activation of oncogenic kinases at intracellular locations is frequently observed in human cancers, but its effects on global signaling are incompletely understood. Here, we show that the oncogenic mutant of Flt3 (Flt3-ITD), when localized at the endoplasmic reticulum (ER), aberrantly activates STAT5 and...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Choudhary C,Olsen JV,Brandts C,Cox J,Reddy PN,Böhmer FD,Gerke V,Schmidt-Arras DE,Berdel WE,Müller-Tidow C,Mann M,Serve H

    更新日期:2009-10-23 00:00:00

  • A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends.

    abstract::The mechanisms by which telomeres are distinguished from DNA double-strand breaks are poorly understood. Here we have defined the minimal requirements for the protection of telomeric DNA ends from nonhomologous end-joining (NHEJ). Neither long, single-stranded overhangs nor t loop formation is essential to prevent NHE...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Bae NS,Baumann P

    更新日期:2007-05-11 00:00:00

  • Genome-wide methylation profiles reveal quantitative views of human aging rates.

    abstract::The ability to measure human aging from molecular profiles has practical implications in many fields, including disease prevention and treatment, forensics, and extension of life. Although chronological age has been linked to changes in DNA methylation, the methylome has not yet been used to measure and compare human ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Hannum G,Guinney J,Zhao L,Zhang L,Hughes G,Sadda S,Klotzle B,Bibikova M,Fan JB,Gao Y,Deconde R,Chen M,Rajapakse I,Friend S,Ideker T,Zhang K

    更新日期:2013-01-24 00:00:00

  • The structure of the bacteriophage PRD1 spike sheds light on the evolution of viral capsid architecture.

    abstract::Comparisons of bacteriophage PRD1 and adenovirus protein structures and virion architectures have been instrumental in unraveling an evolutionary relationship and have led to a proposal of a phylogeny-based virus classification. The structure of the PRD1 spike protein P5 provides further insight into the evolution of ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Merckel MC,Huiskonen JT,Bamford DH,Goldman A,Tuma R

    更新日期:2005-04-15 00:00:00

  • Missing the Mark: PRDM9-Dependent Methylation Is Required for Meiotic DSB Targeting.

    abstract::PRDM9 determines the localization of meiotic recombination hotspots, which are associated with histone H3 methylation. It is not known whether PRDM9's methyltransferase activity is required or how some PRDM9 alleles can dominate the distribution of hotspots over other alleles. Diagouraga, Clément, and colleagues (2018...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Kang R,Zelazowski MJ,Cole F

    更新日期:2018-03-01 00:00:00

  • A global profile of germline gene expression in C. elegans.

    abstract::We used DNA microarrays to profile gene expression patterns in the C. elegans germline and identified 1416 germline-enriched transcripts that define three groups. The sperm-enriched group contains an unusually large number of protein kinases and phosphatases. The oocyte-enriched group includes potentially new componen...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Reinke V,Smith HE,Nance J,Wang J,Van Doren C,Begley R,Jones SJ,Davis EB,Scherer S,Ward S,Kim SK

    更新日期:2000-09-01 00:00:00

  • RNA polymerase I contains a TFIIF-related DNA-binding subcomplex.

    abstract::The eukaryotic RNA polymerases Pol I, II, and III use different promoters to transcribe different classes of genes. Promoter usage relies on initiation factors, including TFIIF and TFIIE, in the case of Pol II. Here, we show that the Pol I-specific subunits A49 and A34.5 form a subcomplex that binds DNA and is related...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Geiger SR,Lorenzen K,Schreieck A,Hanecker P,Kostrewa D,Heck AJ,Cramer P

    更新日期:2010-08-27 00:00:00

  • A Rapid Induction Mechanism for Lin28a in Trophic Responses.

    abstract::Environmental cues provoke rapid transitions in gene expression to support growth and cellular plasticity through incompletely understood mechanisms. Lin28 RNA-binding proteins have evolutionarily conserved roles in post-transcriptional coordination of pro-growth gene expression, but signaling pathways allowing trophi...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Amen AM,Ruiz-Garzon CR,Shi J,Subramanian M,Pham DL,Meffert MK

    更新日期:2017-02-02 00:00:00

  • Global Mapping of Human RNA-RNA Interactions.

    abstract::The majority of the human genome is transcribed into non-coding (nc)RNAs that lack known biological functions or else are only partially characterized. Numerous characterized ncRNAs function via base pairing with target RNA sequences to direct their biological activities, which include critical roles in RNA processing...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Sharma E,Sterne-Weiler T,O'Hanlon D,Blencowe BJ

    更新日期:2016-05-19 00:00:00

  • Telomerase and ATM/Tel1p protect telomeres from nonhomologous end joining.

    abstract::Telomeres protect chromosome ends from fusing to double-stranded breaks (DSBs). Using a quantitative real-time PCR assay, we show that nonhomologous end joining between a telomere and an inducible DSB was undetectable in wild-type cells, but occurred within a few hours of DSB induction in approximately 1/2000 genomes ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Chan SW,Blackburn EH

    更新日期:2003-05-01 00:00:00