当前位置： SCI文献检索 > MOLECULAR CELL期刊下所有文献 > Noncooperative interactions between transcription factors and clustered DNA binding sites enable graded transcriptional responses to environmental inputs.

Noncooperative interactions between transcription factors and clustered DNA binding sites enable graded transcriptional responses to environmental inputs.

Abstract：

:A paradigm in transcriptional regulation is that graded increases in transcription factor (TF) concentration are translated into on/off transcriptional responses by cooperative TF binding to adjacent sites. Digital transcriptional responses underlie the definition of anatomical boundaries during development. Here we show that NF-kappaB, a TF controlling inflammation and immunity, is conversely an analog transcriptional regulator that uses clustered binding sites noncooperatively. We observed that increasing concentrations of NF-kappaB are translated into gradual increments in gene transcription. We provide a thermodynamic interpretation of the experimental observations by combining quantitative measurements and a minimal physical model of an NF-kappaB-dependent promoter. We demonstrate that NF-kappaB binds independently to adjacent sites to promote additive RNA Pol II recruitment and graded transcriptional outputs. These findings reveal an alternative mode of operation of clustered TF binding sites, which might function in biological conditions where the transcriptional output is proportional to the strength of an environmental input.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Giorgetti L,Siggers T,Tiana G,Caprara G,Notarbartolo S,Corona T,Pasparakis M,Milani P,Bulyk ML,Natoli G

doi

10.1016/j.molcel.2010.01.016

subject

Has Abstract

pub_date

2010-02-12 00:00:00

pages

418-28

issue

3

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(10)00045-6

journal_volume

37

pub_type

杂志文章

相关文献

MOLECULAR CELL文献大全
  • Fragile X mental retardation protein and the ribosome.

    abstract：:In this issue of Molecular Cell, Chen et al. (2014) provide evidence that FMRP represses translation by binding the ribosome, suggesting a novel form of translational control. ...

    journal_title：Molecular cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.molcel.2014.04.027

    authors： Harigaya Y,Parker R

    更新日期：2014-05-08 00:00:00

  • MeCP2 binding to DNA depends upon hydration at methyl-CpG.

    abstract：:MeCP2 is an essential transcriptional repressor that mediates gene silencing through binding to methylated DNA. Binding specificity has been thought to depend on hydrophobic interactions between cytosine methyl groups and a hydrophobic patch within the methyl-CpG-binding domain (MBD). X-ray analysis of a methylated DN...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2007.12.028

    authors： Ho KL,McNae IW,Schmiedeberg L,Klose RJ,Bird AP,Walkinshaw MD

    更新日期：2008-02-29 00:00:00

  • Spt6 Association with RNA Polymerase II Directs mRNA Turnover During Transcription.

    abstract：:Spt6 is an essential histone chaperone that mediates nucleosome reassembly during gene transcription. Spt6 also associates with RNA polymerase II (RNAPII) via a tandem Src2 homology domain. However, the significance of Spt6-RNAPII interaction is not well understood. Here, we show that Spt6 recruitment to genes and the...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2018.05.020

    authors： Dronamraju R,Hepperla AJ,Shibata Y,Adams AT,Magnuson T,Davis IJ,Strahl BD

    更新日期：2018-06-21 00:00:00

  • Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction.

    abstract：:The liver plays a central role in the control of glucose homeostasis and is subject to complex regulation by substrates, insulin, and other hormones. To investigate the effect of the loss of direct insulin action in liver, we have used the Cre-loxP system to inactivate the insulin receptor gene in hepatocytes. Liver-s...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：

    authors： Michael MD,Kulkarni RN,Postic C,Previs SF,Shulman GI,Magnuson MA,Kahn CR

    更新日期：2000-07-01 00:00:00

  • The plug domain of the SecY protein stabilizes the closed state of the translocation channel and maintains a membrane seal.

    abstract：:Proteins are translocated across membranes through a channel that is formed by the prokaryotic SecY or eukaryotic Sec61 complex. The crystal structure of the SecY channel from M. jannaschii revealed a plug domain that appears to seal the channel in its closed state. However, the role of the plug remains unclear, parti...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2007.05.002

    authors： Li W,Schulman S,Boyd D,Erlandson K,Beckwith J,Rapoport TA

    更新日期：2007-05-25 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

    doi：10.1016/j.molcel.2010.06.021

    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

  • Uncoupling of sister replisomes during eukaryotic DNA replication.

    abstract：:The duplication of eukaryotic genomes involves the replication of DNA from multiple origins of replication. In S phase, two sister replisomes assemble at each active origin, and they replicate DNA in opposite directions. Little is known about the functional relationship between sister replisomes. Some data imply that ...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2010.11.027

    authors： Yardimci H,Loveland AB,Habuchi S,van Oijen AM,Walter JC

    更新日期：2010-12-10 00:00:00

  • Aurora A on the mitotic spindle is activated by the way it holds its partner.

    abstract：:An exciting study in this issue reveals how binding of the microtubule associated protein TPX2 to the mitotic kinase Aurora A induces a conformational change. This moves the phosphorylated activation domain into a more compact position within the kinase core, providing a better substrate binding platform and hiding th...

    journal_title：Molecular cell

    pub_type： 评论,杂志文章,评审

    doi：10.1016/s1097-2765(03)00405-2

    authors： Glover DM

    更新日期：2003-10-01 00:00:00

  • Nuclear RNA Exosome at 3.1 Å Reveals Substrate Specificities, RNA Paths, and Allosteric Inhibition of Rrp44/Dis3.

    abstract：:The eukaryotic RNA exosome is an essential and conserved 3'-to-5' exoribonuclease complex that degrades or processes nearly every class of cellular RNA. The nuclear RNA exosome includes a 9-subunit non-catalytic core that binds Rrp44 (Dis3) and Rrp6 subunits to modulate their processive and distributive 3'-to-5' exori...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2016.09.038

    authors： Zinder JC,Wasmuth EV,Lima CD

    更新日期：2016-11-17 00:00:00

  • Summon SUMO to wrestle with inflammation.

    abstract：:In this issue of Molecular Cell, Lee et al. (2009) report that SUMOylation of nuclear receptors LXRalpha and LXRbeta plays a critical role in the transrepression of IFN-gamma-induced STAT1-dependent inflammatory responses in brain astrocytes. ...

    journal_title：Molecular cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.molcel.2009.09.002

    authors： Liu B,Shuai K

    更新日期：2009-09-24 00:00:00

  • A role for SIRT1 in the hypoxic response.

    abstract：:In this issue of Molecular Cell, Lim et al. (2010) show that SIRT1 deacetylates HIF-1alpha and regulates its ability to respond to hypoxia, revealing yet another important function of SIRT1 and suggesting a connection between HIF function in aging and sirtuin enzymes. ...

    journal_title：Molecular cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.molcel.2010.06.015

    authors： Leiser SF,Kaeberlein M

    更新日期：2010-06-25 00:00:00

  • Control of actin turnover by a salmonella invasion protein.

    abstract：:Salmonella force their way into nonphagocytic host intestinal cells to initiate infection. Uptake is triggered by delivery into the target cell of bacterial effector proteins that stimulate cytoskeletal rearrangements and membrane ruffling. The Salmonella invasion protein A (SipA) effector is an actin binding protein ...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(04)00053-x

    authors： McGhie EJ,Hayward RD,Koronakis V

    更新日期：2004-02-27 00:00:00

  • Quantifying ubiquitin signaling.

    abstract：:Ubiquitin (UB)-driven signaling systems permeate biology, and are often integrated with other types of post-translational modifications (PTMs), including phosphorylation. Flux through such pathways is dictated by the fractional stoichiometry of distinct modifications and protein assemblies as well as the spatial organ...

    journal_title：Molecular cell

    pub_type： 杂志文章,评审

    doi：10.1016/j.molcel.2015.02.020

    authors： Ordureau A,Münch C,Harper JW

    更新日期：2015-05-21 00:00:00

  • A structurally unique E2-binding domain activates ubiquitination by the ERAD E2, Ubc7p, through multiple mechanisms.

    abstract：:Cue1p is an integral component of yeast endoplasmic reticulum (ER)-associated degradation (ERAD) ubiquitin ligase (E3) complexes. It tethers the ERAD ubiquitin-conjugating enzyme (E2), Ubc7p, to the ER and prevents its degradation, and also activates Ubc7p via unknown mechanisms. We have now determined the crystal str...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2013.04.004

    authors： Metzger MB,Liang YH,Das R,Mariano J,Li S,Li J,Kostova Z,Byrd RA,Ji X,Weissman AM

    更新日期：2013-05-23 00:00:00

  • Telomeres thrown for a loop.

    abstract：:A remarkable paper from the de Lange lab (Wang et al., 2004) in a recent issue of Cell reveals that homologous recombination can result in the abrupt shortening of telomeres in a process that appears to involve reciprocal crossing over within the t-loop structure that protects chromosome ends. ...

    journal_title：Molecular cell

    pub_type： 评论,杂志文章

    doi：10.1016/j.molcel.2004.11.006

    authors： Haber JE

    更新日期：2004-11-19 00:00:00

  • Structural Basis of Transcription Inhibition by Fidaxomicin (Lipiarmycin A3).

    abstract：:Fidaxomicin is an antibacterial drug in clinical use for treatment of Clostridium difficile diarrhea. The active ingredient of fidaxomicin, lipiarmycin A3 (Lpm), functions by inhibiting bacterial RNA polymerase (RNAP). Here we report a cryo-EM structure of Mycobacterium tuberculosis RNAP holoenzyme in complex with Lpm...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2018.02.026

    authors： Lin W,Das K,Degen D,Mazumder A,Duchi D,Wang D,Ebright YW,Ebright RY,Sineva E,Gigliotti M,Srivastava A,Mandal S,Jiang Y,Liu Y,Yin R,Zhang Z,Eng ET,Thomas D,Donadio S,Zhang H,Zhang C,Kapanidis AN,Ebright RH

    更新日期：2018-04-05 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

  • Transient DNA Occupancy of the SMC Interarm Space in Prokaryotic Condensin.

    abstract：:Multi-subunit SMC ATPases control chromosome superstructure and DNA topology, presumably by DNA translocation and loop extrusion. Chromosomal DNA is entrapped within the tripartite SMCkleisin ring. Juxtaposed SMC heads ("J heads") or engaged SMC heads ("E heads") split the SMCkleisin ring into "S" and "K" sub-compartm...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2019.05.001

    authors： Vazquez Nunez R,Ruiz Avila LB,Gruber S

    更新日期：2019-07-25 00:00:00

  • Molecular mechanism for the regulation of protein kinase B/Akt by hydrophobic motif phosphorylation.

    abstract：:Protein kinase B/Akt plays crucial roles in promoting cell survival and mediating insulin responses. The enzyme is stimulated by phosphorylation at two regulatory sites: Thr 309 of the activation segment and Ser 474 of the hydrophobic motif, a conserved feature of many AGC kinases. Analysis of the crystal structures o...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(02)00550-6

    authors： Yang J,Cron P,Thompson V,Good VM,Hess D,Hemmings BA,Barford D

    更新日期：2002-06-01 00:00:00

  • Rewiring mitochondrial pyruvate metabolism: switching off the light in cancer cells?

    abstract：:Metabolic reprogramming is a characteristic of cancer cells. Three studies published in this month's Molecular Cell provide novel insights into the role of mitochondrial pyruvate in tumor metabolism and describe how targeting pyruvate transport and metabolism may afford therapeutic benefit. ...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2014.10.018

    authors： Szlosarek PW,Lee S,Pollard PJ

    更新日期：2014-11-06 00:00:00

  • Regulation of apoptosis by alternative pre-mRNA splicing.

    abstract：:Apoptosis, a phenomenon that allows the regulated destruction and disposal of damaged or unwanted cells, is common to many cellular processes in multicellular organisms. In humans more than 200 proteins are involved in apoptosis, many of which are dysregulated or defective in human diseases including cancer. A large n...

    journal_title：Molecular cell

    pub_type： 杂志文章,评审

    doi：10.1016/j.molcel.2005.05.026

    authors： Schwerk C,Schulze-Osthoff K

    更新日期：2005-07-01 00:00:00

  • Mitochondrial NAD+ Controls Nuclear ARTD1-Induced ADP-Ribosylation.

    abstract：:In addition to its role as an electron transporter, mitochondrial nicotinamide adenine dinucleotide (NAD+) is an important co-factor for enzymatic reactions, including ADP-ribosylation. Although mitochondria harbor the most intra-cellular NAD+, mitochondrial ADP-ribosylation remains poorly understood. Here we provide ...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2020.12.034

    authors： Hopp AK,Teloni F,Bisceglie L,Gondrand C,Raith F,Nowak K,Muskalla L,Howald A,Pedrioli PGA,Johnsson K,Altmeyer M,Pedrioli DML,Hottiger MO

    更新日期：2021-01-21 00:00:00

  • Rhythmic PER abundance defines a critical nodal point for negative feedback within the circadian clock mechanism.

    abstract：:Circadian rhythms in mammals are generated by a transcriptional negative feedback loop that is driven primarily by oscillations of PER and CRY, which inhibit their own transcriptional activators, CLOCK and BMAL1. Current models posit that CRY is the dominant repressor, while PER may play an accessory role. In this stu...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2009.10.012

    authors： Chen R,Schirmer A,Lee Y,Lee H,Kumar V,Yoo SH,Takahashi JS,Lee C

    更新日期：2009-11-13 00:00:00

  • Crystal structure of the PP2A phosphatase activator: implications for its PP2A-specific PPIase activity.

    abstract：:PTPA, an essential and specific activator of protein phosphatase 2A (PP2A), functions as a peptidyl prolyl isomerase (PPIase). We present here the crystal structures of human PTPA and of the two yeast orthologs (Ypa1 and Ypa2), revealing an all alpha-helical protein fold that is radically different from other PPIases....

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2006.07.008

    authors： Leulliot N,Vicentini G,Jordens J,Quevillon-Cheruel S,Schiltz M,Barford D,van Tilbeurgh H,Goris J

    更新日期：2006-08-04 00:00:00

  • The yeast G protein alpha subunit Gpa1 transmits a signal through an RNA binding effector protein Scp160.

    abstract：:In yeast Saccharomyces cerevisiae the G protein betagamma subunits (Ste4/Ste18) have long been known to transmit the signal required for mating. Here we demonstrate that GTPase-deficient mutants of Galpha (Gpa1) directly activate the mating response pathway. We also show that signaling by activated Gpa1 requires direc...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(03)00307-1

    authors： Guo M,Aston C,Burchett SA,Dyke C,Fields S,Rajarao SJ,Uetz P,Wang Y,Young K,Dohlman HG

    更新日期：2003-08-01 00:00:00

  • The pathway for DNA recognition and RNA integration by a group II intron retrotransposon.

    abstract：:Group II intron RNPs are mobile genetic elements that attack and invade duplex DNA. In this work, we monitor the invasion reaction in vitro and establish a quantitative kinetic framework for the steps of this complex cascade. We find that target site specificity is achieved after DNA binding, which occurs nonspecifica...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(03)00069-8

    authors： Aizawa Y,Xiang Q,Lambowitz AM,Pyle AM

    更新日期：2003-03-01 00:00:00

  • Introns Protect Eukaryotic Genomes from Transcription-Associated Genetic Instability.

    abstract：:Transcription is a source of genetic instability that can notably result from the formation of genotoxic DNA:RNA hybrids, or R-loops, between the nascent mRNA and its template. Here we report an unexpected function for introns in counteracting R-loop accumulation in eukaryotic genomes. Deletion of endogenous introns i...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2017.07.002

    authors： Bonnet A,Grosso AR,Elkaoutari A,Coleno E,Presle A,Sridhara SC,Janbon G,Géli V,de Almeida SF,Palancade B

    更新日期：2017-08-17 00:00:00

  • Meiotic recombination remote from prominent DNA break sites in S. pombe.

    abstract：:DNA breakage is intimately associated with meiotic recombination in the fission yeast Schizosaccharomyces pombe. Sites of prominent DNA breakage were found approximately 25 to approximately 200 kb apart in the genomic regions surveyed. We examined in detail a 501 kb region of chromosome I and found six sites, or tight...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/s1097-2765(02)00452-5

    authors： Young JA,Schreckhise RW,Steiner WW,Smith GR

    更新日期：2002-02-01 00:00:00

  • Destabilizing LSD1 by Jade-2 promotes neurogenesis: an antibraking system in neural development.

    abstract：:Histone H3K4 demethylase LSD1 plays an important role in stem cell biology, especially in the maintenance of the silencing of differentiation genes. However, how the function of LSD1 is regulated and the differentiation genes are derepressed are not understood. Here, we report that elimination of LSD1 promotes embryon...

    journal_title：Molecular cell

    pub_type： 杂志文章

    doi：10.1016/j.molcel.2014.06.006

    authors： Han X,Gui B,Xiong C,Zhao L,Liang J,Sun L,Yang X,Yu W,Si W,Yan R,Yi X,Zhang D,Li W,Li L,Yang J,Wang Y,Sun YE,Zhang D,Meng A,Shang Y

    更新日期：2014-08-07 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

    doi：10.1016/s1097-2765(03)00436-2

    authors： Fazzio TG,Tsukiyama T

    更新日期：2003-11-01 00:00:00