当前位置： SCI文献检索 > MOLECULAR CELL期刊下所有文献 > PRDM16 Suppresses MLL1r Leukemia via Intrinsic Histone Methyltransferase Activity.

PRDM16 Suppresses MLL1r Leukemia via Intrinsic Histone Methyltransferase Activity.

Abstract：

:PRDM16 is a transcription co-factor that plays critical roles in development of brown adipose tissue, as well as maintenance of adult hematopoietic and neural stem cells. Here we report that PRDM16 is a histone H3K4 methyltransferase on chromatin. Mutation in the N-terminal PR domain of PRDM16 abolishes the intrinsic enzymatic activity of PRDM16. We show that the methyltransferase activity of PRDM16 is required for specific suppression of MLL fusion protein-induced leukemogenesis both in vitro and in vivo. Mechanistic studies show that PRDM16 directly activates the SNAG family transcription factor Gfi1b, which in turn downregulates the HOXA gene cluster. Knockdown Gfi1b represses PRDM16-mediated tumor suppression, while Gfi1b overexpression mimics PRDM16 overexpression. In further support of the tumor suppressor function of PRDM16, silencing PRDM16 by DNA methylation is concomitant with MLL-AF9-induced leukemic transformation. Taken together, our study reveals a previously uncharacterized function of PRDM16 that depends on its PR domain activity.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Zhou B,Wang J,Lee SY,Xiong J,Bhanu N,Guo Q,Ma P,Sun Y,Rao RC,Garcia BA,Hess JL,Dou Y

doi

10.1016/j.molcel.2016.03.010

subject

Has Abstract

pub_date

2016-04-21 00:00:00

pages

222-236

issue

2

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(16)00188-X

journal_volume

62

pub_type

杂志文章

相关文献

MOLECULAR CELL文献大全
  • yTAFII61 has a general role in RNA polymerase II transcription and is required by Gcn4p to recruit the SAGA coactivator complex.

    abstract：:We obtained a recessive insertion mutation in the gene encoding yeast TBP-associated factor yTAFII61/68 that impairs Gcn4p-independent and Gcn4p-activated HIS3 transcription. This mutation also reduces transcription of seven other class II genes, thus indicating a broad role for this yTAFII in RNA polymerase II transc...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(00)80166-5

    authors： Natarajan K,Jackson BM,Rhee E,Hinnebusch AG

    更新日期：1998-11-01 00:00:00

  • HATs off to PIC assembly.

    abstract：:There are many regulated steps in the assembly of a transcription preinitiation complex (PIC). In this issue of Molecular Cell, Black et. al. (2006) reveal a catalytic switch mechanism in which autoacetylation of the HAT p300 triggers its dissociation from a promoter in a manner that is coupled to TFIID association. ...

    journal_title：Molecular cell

    pub_type： 评论,杂志文章,评审

    doi：10.1016/j.molcel.2006.08.022

    authors： Pugh BF

    更新日期：2006-09-15 00:00:00

  • Antibiotic-induced bacterial cell death exhibits physiological and biochemical hallmarks of apoptosis.

    abstract：:Programmed cell death is a gene-directed process involved in the development and homeostasis of multicellular organisms. The most common mode of programmed cell death is apoptosis, which is characterized by a stereotypical set of biochemical and morphological hallmarks. Here we report that Escherichia coli also exhibi...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2012.04.027

    authors： Dwyer DJ,Camacho DM,Kohanski MA,Callura JM,Collins JJ

    更新日期：2012-06-08 00:00:00

  • Functions of Replication Protein A as a Sensor of R Loops and a Regulator of RNaseH1.

    abstract：:R loop, a transcription intermediate containing RNA:DNA hybrids and displaced single-stranded DNA (ssDNA), has emerged as a major source of genomic instability. RNaseH1, which cleaves the RNA in RNA:DNA hybrids, plays an important role in R loop suppression. Here we show that replication protein A (RPA), an ssDNA-bind...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2017.01.029

    authors： Nguyen HD,Yadav T,Giri S,Saez B,Graubert TA,Zou L

    更新日期：2017-03-02 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

    doi：10.1016/j.molcel.2007.02.025

    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

  • Transcriptional ShortCUTs.

    abstract：:Recent work from Kuehner and Brow (2008) and Thiebaut et al. (2008) in Molecular Cell and Jenks et al. (2008) in Molecular and Cellular Biology reveals that regulated expression of central nucleotide synthesis pathway components directs start site-dependent RNA polymerase II termination. ...

    journal_title：Molecular cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.molcel.2008.08.014

    authors： Dichtl B

    更新日期：2008-09-05 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

    doi：10.1016/j.molcel.2017.10.023

    authors： Rao AN,Cooper TA

    更新日期：2017-11-02 00:00:00

  • Structure and mechanism of RNA polymerase II CTD phosphatases.

    abstract：:Recycling of RNA polymerase II (Pol II) after transcription requires dephosphorylation of the polymerase C-terminal domain (CTD) by the phosphatase Fcp1. We report the X-ray structure of the small CTD phosphatase Scp1, which is homologous to the Fcp1 catalytic domain. The structure shows a core fold and an active cent...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2004.06.035

    authors： Kamenski T,Heilmeier S,Meinhart A,Cramer P

    更新日期：2004-08-13 00:00:00

  • Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis.

    abstract：:The role of the protein kinase Akt in cell migration is incompletely understood. Here we show that sphingosine-1-phosphate (S1P)-induced endothelial cell migration requires the Akt-mediated phosphorylation of the G protein-coupled receptor (GPCR) EDG-1. Activated Akt binds to EDG-1 and phosphorylates the third intrace...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(01)00324-0

    authors： Lee MJ,Thangada S,Paik JH,Sapkota GP,Ancellin N,Chae SS,Wu M,Morales-Ruiz M,Sessa WC,Alessi DR,Hla T

    更新日期：2001-09-01 00:00:00

  • Identification of a tRNA-specific nuclear export receptor.

    abstract：:In eukaryotes, tRNAs are synthesized in the nucleus and after several maturation steps exported to the cytoplasm. Here, we identify exportin-t as a specific mediator of tRNA export. It is a RanGTP-binding, importin beta-related factor with predominantly nuclear localization. It shuttles rapidly between nucleus and cyt...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(00)80036-2

    authors： Kutay U,Lipowsky G,Izaurralde E,Bischoff FR,Schwarzmaier P,Hartmann E,Görlich D

    更新日期：1998-02-01 00:00:00

  • Coupling of ribosomal L1 stalk and tRNA dynamics during translation elongation.

    abstract：:By using single-molecule fluorescence resonance energy transfer (smFRET), we observe the real-time dynamic coupling between the ribosome, labeled at the L1 stalk, and transfer RNA (tRNA). We find that an interaction between the ribosomal L1 stalk and the newly deacylated tRNA is established spontaneously upon peptide ...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2008.03.012

    authors： Fei J,Kosuri P,MacDougall DD,Gonzalez RL Jr

    更新日期：2008-05-09 00:00:00

  • Prolyl cis-trans Isomerization as a molecular timer in Crk signaling.

    abstract：:In a recent issue of Molecular Cell, use NMR to identify peptidyl-prolyl cis-trans isomerization as an autoinhibitory switch in the adaptor protein Crk, suggesting a new mechanism for controlling the rate of formation of signaling complexes. ...

    journal_title：Molecular cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.molcel.2007.02.005

    authors： Nicholson LK,Lu KP

    更新日期：2007-02-23 00:00:00

  • The actin-bundling protein palladin is an Akt1-specific substrate that regulates breast cancer cell migration.

    abstract：:The phosphatidylinositol 3-kinase (PI3K) signaling pathway is frequently deregulated in cancer. Downstream of PI3K, Akt1 and Akt2 have opposing roles in breast cancer invasive migration, leading to metastatic dissemination. Here, we identify palladin, an actin-associated protein, as an Akt1-specific substrate that mod...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2010.02.031

    authors： Chin YR,Toker A

    更新日期：2010-05-14 00:00:00

  • Functional interdependence at the chromatin level between the MKK6/p38 and IGF1/PI3K/AKT pathways during muscle differentiation.

    abstract：:During muscle regeneration, the mechanism integrating environmental cues at the chromatin of muscle progenitors is unknown. We show that inflammation-activated MKK6-p38 and insulin growth factor 1 (IGF1)-induced PI3K/AKT pathways converge on the chromatin of muscle genes to target distinct components of the muscle tra...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2007.08.021

    authors： Serra C,Palacios D,Mozzetta C,Forcales SV,Morantte I,Ripani M,Jones DR,Du K,Jhala US,Simone C,Puri PL

    更新日期：2007-10-26 00:00:00

  • The structure of a receptor with two associating transmembrane domains on the cell surface: integrin alphaIIbbeta3.

    abstract：:Structures of intact receptors with single-pass transmembrane domains are essential to understand how extracellular and cytoplasmic domains regulate association and signaling through transmembrane domains. A chemical and computational method to determine structures of the membrane regions of such receptors on the cell...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2009.02.022

    authors： Zhu J,Luo BH,Barth P,Schonbrun J,Baker D,Springer TA

    更新日期：2009-04-24 00:00:00

  • PINK1 Phosphorylates MIC60/Mitofilin to Control Structural Plasticity of Mitochondrial Crista Junctions.

    abstract：:Mitochondrial crista structure partitions vital cellular reactions and is precisely regulated by diverse cellular signals. Here, we show that, in Drosophila, mitochondrial cristae undergo dynamic remodeling among distinct subcellular regions and the Parkinson's disease (PD)-linked Ser/Thr kinase PINK1 participates in ...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2018.01.026

    authors： Tsai PI,Lin CH,Hsieh CH,Papakyrikos AM,Kim MJ,Napolioni V,Schoor C,Couthouis J,Wu RM,Wszolek ZK,Winter D,Greicius MD,Ross OA,Wang X

    更新日期：2018-03-01 00:00:00

  • β-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4.

    abstract：:β-hydroxybutyrate (β-HB) elevation during fasting or caloric restriction is believed to induce anti-aging effects and alleviate aging-related neurodegeneration. However, whether β-HB alters the senescence pathway in vascular cells remains unknown. Here we report that β-HB promotes vascular cell quiescence, which signi...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2018.07.036

    authors： Han YM,Bedarida T,Ding Y,Somba BK,Lu Q,Wang Q,Song P,Zou MH

    更新日期：2018-09-20 00:00:00

  • MeCP2 Represses Enhancers through Chromosome Topology-Associated DNA Methylation.

    abstract：:The genomes of mammalian neurons contain uniquely high levels of non-CG DNA methylation that can be bound by the Rett syndrome protein, MeCP2, to regulate gene expression. How patterns of non-CG methylation are established in neurons and the mechanism by which this methylation works with MeCP2 to control gene expressi...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2019.10.033

    authors： Clemens AW,Wu DY,Moore JR,Christian DL,Zhao G,Gabel HW

    更新日期：2020-01-16 00:00:00

  • Generating crossovers by resolution of nicked Holliday junctions: a role for Mus81-Eme1 in meiosis.

    abstract：:The double Holliday junction (dHJ) is generally regarded to be a key intermediate of meiotic recombination, whose resolution is critical for the formation of crossover recombinants. In fission yeast, the Mus81-Eme1 endonuclease has been implicated in resolving dHJs. Consistent with this role, we show that Mus81-Eme1 i...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(03)00343-5

    authors： Osman F,Dixon J,Doe CL,Whitby MC

    更新日期：2003-09-01 00:00:00

  • Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous Recombination and Genome Stability.

    abstract：:XPG is a structure-specific endonuclease required for nucleotide excision repair, and incision-defective XPG mutations cause the skin cancer-prone syndrome xeroderma pigmentosum. Truncating mutations instead cause the neurodevelopmental progeroid disorder Cockayne syndrome, but little is known about how XPG loss resul...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2015.12.026

    authors： Trego KS,Groesser T,Davalos AR,Parplys AC,Zhao W,Nelson MR,Hlaing A,Shih B,Rydberg B,Pluth JM,Tsai MS,Hoeijmakers JHJ,Sung P,Wiese C,Campisi J,Cooper PK

    更新日期：2016-02-18 00:00:00

  • Controlling cytokinesis through promiscuous phosphorylation outside BARs.

    abstract：:In this issue of Molecular Cell, Roberts-Galbraith and colleagues report that a key cytokinetic regulator in fission yeast, Cdc15, is phosphorylated on numerous sites that collectively, but not individually, control its oligomerization state and its associations with the plasma membrane and interacting proteins. ...

    journal_title：Molecular cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.molcel.2010.06.028

    authors： Glotzer M

    更新日期：2010-07-09 00:00:00

  • pRB contains an E2F1-specific binding domain that allows E2F1-induced apoptosis to be regulated separately from other E2F activities.

    abstract：:The interaction between pRB and E2F is critical for control of the cell cycle and apoptosis. Here we report that pRB contains two distinct E2F binding sites. The previously identified E2F binding site on pRB is necessary for stable association with E2Fs on DNA. A second E2F interaction site is located entirely within ...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(03)00344-7

    authors： Dick FA,Dyson N

    更新日期：2003-09-01 00:00:00

  • Cap-assisted internal initiation of translation of histone H4.

    abstract：:In eukaryotes, a crucial step of translation initiation is the binding of the multifactor complex eIF4F to the 5' end of the mRNA, a prerequisite to recruitment of the activated small ribosomal 43S particle. Histone H4 mRNAs have short 5'UTRs, which do not conform to the conventional scanning-initiation model. Here we...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2010.12.019

    authors： Martin F,Barends S,Jaeger S,Schaeffer L,Prongidi-Fix L,Eriani G

    更新日期：2011-01-21 00:00:00

  • Srs2 disassembles Rad51 filaments by a protein-protein interaction triggering ATP turnover and dissociation of Rad51 from DNA.

    abstract：:Rad51 is a DNA recombinase functioning in the repair of DNA double-strand breaks and the generation of genetic diversity by homologous recombination (HR). In the presence of ATP, Rad51 self-assembles into an extended polymer on single-stranded DNA to catalyze strand exchange. Inappropriate HR causes genomic instabilit...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2009.05.026

    authors： Antony E,Tomko EJ,Xiao Q,Krejci L,Lohman TM,Ellenberger T

    更新日期：2009-07-10 00:00:00

  • CDC16 controls initiation at chromosome replication origins.

    abstract：:The Cdc28p cyclin-dependent kinase is thought to both catalyze the onset of DNA replication and prevent rereplication by blocking the reassembly of initiation complexes at replication origins. Budding yeast with mutations in the CDC16 gene represent an exception to this model, because they rereplicate DNA despite bein...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(00)80046-5

    authors： Heichman KA,Roberts JM

    更新日期：1998-02-01 00:00:00

  • Smad about E2F. TGFbeta repressionof c-Myc via a Smad3/E2F/p107 complex.

    abstract：:Signaling by TGFbeta regulates the expression of hundreds of genes. The rapid repression of c-Myc stands out because of its roles in growth control and cancer. Recent work shows that c-Myc repression by TGFbeta is mediated by the nuclear translocation of a novel, preformed complex composed of Smad3, E2F4 or E2F5, and ...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(02)00584-1

    authors： Kowalik TF

    更新日期：2002-07-01 00:00:00

  • Multidomain Convergence of Argonaute during RISC Assembly Correlates with the Formation of Internal Water Clusters.

    abstract：:Despite the relevance of Argonaute proteins in RNA silencing, little is known about the structural steps of small RNA loading to form RNA-induced silencing complexes (RISCs). We report the 1.9 Å crystal structure of human Argonaute4 with guide RNA. Comparison with the previously determined apo structure of Neurospora ...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2019.06.011

    authors： Park MS,Araya-Secchi R,Brackbill JA,Phan HD,Kehling AC,Abd El-Wahab EW,Dayeh DM,Sotomayor M,Nakanishi K

    更新日期：2019-08-22 00:00:00

  • A 3' exonuclease that specifically interacts with the 3' end of histone mRNA.

    abstract：:Metazoan histone mRNAs end in a highly conserved stem-loop structure followed by ACCCA. Previous studies have suggested that the stem-loop binding protein (SLBP) is the only protein binding this region. Using RNA affinity purification, we identified a second protein, designated 3'hExo, that contains a SAP and a 3' exo...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(03)00278-8

    authors： Dominski Z,Yang XC,Kaygun H,Dadlez M,Marzluff WF

    更新日期：2003-08-01 00:00:00

  • Temporal regulation of RNA polymerase II by Srb10 and Kin28 cyclin-dependent kinases.

    abstract：:Two cyclin-dependent kinases have been identified in yeast and mammalian RNA polymerase II transcription initiation complexes. We find that the two yeast kinases are indistinguishable in their ability to phosphorylate the RNA polymerase II CTD, and yet in living cells one kinase is a positive regulator and the other a...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(00)80112-4

    authors： Hengartner CJ,Myer VE,Liao SM,Wilson CJ,Koh SS,Young RA

    更新日期：1998-07-01 00:00:00

  • Pif1-Family Helicases Support Fork Convergence during DNA Replication Termination in Eukaryotes.

    abstract：:The convergence of two DNA replication forks creates unique problems during DNA replication termination. In E. coli and SV40, the release of torsional strain by type II topoisomerases is critical for converging replisomes to complete DNA synthesis, but the pathways that mediate fork convergence in eukaryotes are unkno...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2019.01.040

    authors： Deegan TD,Baxter J,Ortiz Bazán MÁ,Yeeles JTP,Labib KPM

    更新日期：2019-04-18 00:00:00