Online citations, reference lists, and bibliographies.

Cooperative Transcriptional Activation By Klf4, Meis2, And Pbx1

Glen A Bjerke, Cathy Hyman-Walsh, David Wotton
Published 2011 · Medicine, Biology
Cite This
Download PDF
Analyze on Scholarcy
Share
ABSTRACT The Kruppel-like factor Klf4 is implicated in tumorigenesis and maintaining stem cell pluripotency, and Klf4 can both activate and repress gene expression. We show that the Pbx1 and Meis2 homeodomain proteins interact with Klf4 and can be recruited to DNA elements comprising a Klf4 site or GC box, with adjacent Meis and Pbx sites. Meis2d and Pbx1a activate expression of p15Ink4a and E-cadherin, dependent on the Meis2d transcriptional activation domain. In HepG2 cells, reducing expression of endogenous Meis2 or Pbx1 decreases p15 gene expression and increases the number of cells entering S phase. Although DNA binding by all three proteins contributes to full cooperative activation, the sequence requirements for binding by Meis2 and Pbx1 are variable. In the E-cadherin promoter, a Pbx-like site is required for full activation, whereas in the p15 promoter, the Klf4 site appears to play the major role. Through a bioinformatics search we identified additional genes with conserved binding sites for Klf4, Meis2, and Pbx1 and show that at least some of these genes can be activated cooperatively by Klf4 and Meis2/Pbx1. We suggest a model in which genes with Klf4 sites can be cooperatively activated by Meis2/Pbx1 and Klf4, dependent primarily on recruitment by Klf4. This provides a mechanism to modulate transcriptional regulation by the multifunctional Klf4 transcription factor.
This paper references
10.1074/jbc.270.52.31178
A Novel Homeobox Protein Which Recognizes a TGT Core and Functionally Interferes with a Retinoid-responsive Motif (*)
E. Bertolino (1995)
10.1126/science.3529394
Purification and biochemical characterization of the promoter-specific transcription factor, Sp1.
M. R. Briggs (1986)
10.1016/S0093-3619(08)70913-4
In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state
G.M.P. Galbraith (2008)
10.1101/gad.5.3.358
The human t(1;19) translocation in pre-B ALL produces multiple nuclear E2A-Pbx1 fusion proteins with differing transforming potentials.
Mark P. Kamps (1991)
10.1128/MCB.15.10.5434
Meis1, a PBX1-related homeobox gene involved in myeloid leukemia in BXH-2 mice.
J. Moskow (1995)
10.1016/j.ygeno.2005.01.005
Mammalian SP/KLF transcription factors: bring in the family.
G. Suske (2005)
10.1093/nar/28.5.1106
Transactivation and growth suppression by the gut-enriched Krüppel-like factor (Krüppel-like factor 4) are dependent on acidic amino acid residues and protein-protein interaction.
D. Geiman (2000)
10.1093/nar/26.3.796
Identification of the DNA sequence that interacts with the gut-enriched Krüppel-like factor.
J. M. Shields (1998)
10.1016/S0959-437X(98)80113-5
Hox proteins meet more partners.
R. Mann (1998)
10.1074/jbc.M413963200
MEIS C Termini Harbor Transcriptional Activation Domains That Respond to Cell Signaling*
He Yan Huang (2005)
10.1387/IJDB.072304AL
PBX proteins: much more than Hox cofactors.
Audrey Laurent (2008)
10.1016/0092-8674(87)90594-0
Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain
J. T. Kadonaga (1987)
10.1038/sj.onc.1208307
Induction of KLF4 in basal keratinocytes blocks the proliferation–differentiation switch and initiates squamous epithelial dysplasia
K. Foster (2005)
10.1128/MCB.26.3.990-1001.2006
TGIF Inhibits Retinoid Signaling
Laurent Bartholin (2006)
10.1073/pnas.93.1.470
Selective repression of transcriptional activators by Pbx1 does not require the homeodomain.
Q. Lu (1996)
10.1128/MCB.19.7.5134
Trimeric Association of Hox and TALE Homeodomain Proteins Mediates Hoxb2 Hindbrain Enhancer Activity
Y. Jacobs (1999)
10.1038/17833
Structure of a DNA-bound Ultrabithorax–Extradenticle homeodomain complex
J. M. Passner (1999)
10.1016/j.stem.2007.05.014
Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution.
N. Maherali (2007)
10.1242/dev.022350
Pbx1 functions in distinct regulatory networks to pattern the great arteries and cardiac outflow tract
C. Chang (2008)
Regulation of Hox target genes by a DNA bound Homothorax/Hox/Extradenticle complex.
H. D. Ryoo (1999)
10.1016/0092-8674(83)90210-6
The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter
W. Dynan (1983)
10.1016/0092-8674(94)90292-5
Homeodomain-DNA recognition
W. Gehring (1994)
10.1038/sj.onc.1207067
Identification of Krüppel-like factor 4 as a potential tumor suppressor gene in colorectal cancer
W. Zhao (2004)
10.1093/emboj/17.5.1434
The novel homeoprotein Prep1 modulates Pbx-Hox protein cooperativity.
J. Berthelsen (1998)
10.1111/j.1742-464X.2010.07668.x
An autoinhibitory effect of the homothorax domain of Meis2.
Cathy Hyman-Walsh (2010)
10.1074/jbc.M908382199
Three-amino acid Extension Loop Homeodomain Proteins Meis2 and TGIF Differentially Regulate Transcription*
Y. Yang (2000)
10.1128/MCB.16.4.1734
Pbx modulation of Hox homeodomain amino-terminal arms establishes different DNA-binding specificities across the Hox locus.
C. P. Chang (1996)
Identification of a new family of Pbx-related homeobox genes.
T. Nakamura (1996)
10.1016/J.YDBIO.2007.08.031
The homeodomain transcription factor Prep1 (pKnox1) is required for hematopoietic stem and progenitor cell activity.
Patrizia Di Rosa (2007)
10.1371/journal.pone.0002424
Cytosolic Sequestration of Prep1 Influences Early Stages of T Cell Development
Dmitry Penkov (2008)
10.1111/J.1745-7270.2008.00439.X
Roles of Kruppel-like factor 4 in normal homeostasis, cancer and stem cells
P. M. Evans (2008)
10.1038/35070086
TGFβ influences Myc, Miz-1 and Smad to control the CDK inhibitor p15INK4b
J. Seoane (2001)
10.1128/MCB.25.24.10768-10781.2005
Involvement of Prep1 in the αβ T-Cell Receptor T-Lymphocytic Potential of Hematopoietic Precursors
D. Penkov (2005)
Roles of Krüpel-like factor 4 in normal homeostasis, cancer and stem cells.
Paul Michael Evans (2008)
10.1101/GAD.1602107
Meis1 is an essential and rate-limiting regulator of MLL leukemia stem cell potential.
P. Wong (2007)
10.1593/NEO.91122
Genetic and epigenetic inactivation of Kruppel-like factor 4 in medulloblastoma.
Y. Nakahara (2010)
10.1016/0092-8674(84)90370-2
A homologous protein-coding sequence in drosophila homeotic genes and its conservation in other metazoans
W. McGinnis (1984)
10.1074/jbc.273.2.1026
Human EZF, a Krüppel-like Zinc Finger Protein, Is Expressed in Vascular Endothelial Cells and Contains Transcriptional Activation and Repression Domains*
S. Yet (1998)
10.1186/gb-2003-4-2-206
Sp1- and Krüppel-like transcription factors
J. Kaczynski (2003)
10.1128/MCB.15.10.5811
The pentapeptide motif of Hox proteins is required for cooperative DNA binding with Pbx1, physically contacts Pbx1, and enhances DNA binding by Pbx1.
P. Knoepfler (1995)
10.1128/MCB.19.11.7577
PBX and MEIS as Non-DNA-Binding Partners in Trimeric Complexes with HOX Proteins
K. Shanmugam (1999)
10.1093/nar/30.9.2043
Characterization of PREP2, a paralog of PREP1, which defines a novel sub-family of the MEINOX TALE homeodomain transcription factors.
C. Fognani (2002)
10.1073/pnas.94.26.14553
Meis1 and pKnox1 bind DNA cooperatively with Pbx1 utilizing an interaction surface disrupted in oncoprotein E2a-Pbx1.
P. Knoepfler (1997)
10.1074/jbc.274.52.37105
Multiple Modes of Repression by the Smad Transcriptional Corepressor TGIF*
D. Wotton (1999)
GENERATION OF GERMLINECOMPETENT INDUCED PLURIPOTENT STEM CELLS
K. Okita (2007)
10.1007/s00239-006-0023-0
Comprehensive Analysis of Animal TALE Homeobox Genes: New Conserved Motifs and Cases of Accelerated Evolution
Krishanu Mukherjee (2006)
10.1038/nature05934
Generation of germline-competent induced pluripotent stem cells
K. Okita (2007)
10.1074/jbc.270.45.26750
Transforming Growth Factor β Activates the Promoter of Cyclin-dependent Kinase Inhibitor p15INK4B through an Sp1 Consensus Site (*)
J. Li (1995)
10.1016/S0092-8674(00)80662-5
Structure of a HoxB1–Pbx1 Heterodimer Bound to DNA Role of the Hexapeptide and a Fourth Homeodomain Helix in Complex Formation
D. Piper (1999)
10.1016/S0092-8674(00)80400-6
Nuclear Translocation of Extradenticle Requires homothorax, which Encodes an Extradenticle-Related Homeodomain Protein
G. Rieckhof (1997)
10.1016/0092-8674(90)90658-2
A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B all
M. Kamps (1990)
10.1016/j.devcel.2008.01.004
Genome-wide identification of Smad/Foxh1 targets reveals a role for Foxh1 in retinoic acid regulation and forebrain development.
C. Silvestri (2008)
10.1002/(SICI)1097-0177(199710)210:2<173::AID-AJA9>3.0.CO;2-D
Meis2, a novel mouse Pbx-related homeobox gene induced by retinoic acid during differentiation of P19 embryonal carcinoma cells.
M. Oulad-Abdelghani (1997)
10.1093/nar/25.21.4173
Analysis of TALE superclass homeobox genes (MEIS, PBC, KNOX, Iroquois, TGIF) reveals a novel domain conserved between plants and animals.
T. Bürglin (1997)
10.1101/gad.9.6.663
Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of Hox proteins.
C. P. Chang (1995)
10.1128/MCB.12.10.4251
Cloning of GT box-binding proteins: a novel Sp1 multigene family regulating T-cell receptor gene expression.
C. Kingsley (1992)
10.1210/me.2006-0480
ETV1 is a novel androgen receptor-regulated gene that mediates prostate cancer cell invasion.
Changmeng Cai (2007)
10.1038/sj.onc.1203371
HoxA9-mediated immortalization of myeloid progenitors requires functional interactions with TALE cofactors Pbx and Meis
C. A. Schnabel (2000)
10.1016/j.ydbio.2005.10.032
Hox cofactors in vertebrate development.
C. Moens (2006)
10.1093/nar/26.10.2499
Sp1, but not Sp3, functions to mediate promoter activation by TGF-beta through canonical Sp1 binding sites.
J. Li (1998)
10.1093/emboj/17.5.1423
Prep1, a novel functional partner of Pbx proteins.
J. Berthelsen (1998)
10.1074/jbc.M100678200
DNA Binding and Transcriptional Activation by a PDX1·PBX1b·MEIS2b Trimer and Cooperation with a Pancreas-specific Basic Helix-Loop-Helix Complex*
Y. Liu (2001)
10.1128/MCB.21.1.224-234.2001
Defining Roles for HOX and MEIS1 Genes in Induction of Acute Myeloid Leukemia
U. Thorsteinsdottir (2001)
10.1074/jbc.M103377200
TGIF2 Interacts with Histone Deacetylase 1 and Represses Transcription*
T. Melhuish (2001)
10.1002/bies.20581
The diverse functions of Krüppel-like factors 4 and 5 in epithelial biology and pathobiology.
B. B. McConnell (2007)
10.1016/S1097-2765(04)00260-6
Pbx marks genes for activation by MyoD indicating a role for a homeodomain protein in establishing myogenic potential.
C. Berkes (2004)
10.1074/jbc.M110.114546
Krüppel-like Factor 4 Inhibits Epithelial-to-Mesenchymal Transition through Regulation of E-cadherin Gene Expression*
Jennifer L. Yori (2010)
10.1038/308428a0
A conserved DNA sequence in homoeotic genes of the Drosophila Antennapedia and bithorax complexes
W. McGinnis (1984)
10.1093/nar/27.18.3752
A conserved motif N-terminal to the DNA-binding domains of myogenic bHLH transcription factors mediates cooperative DNA binding with pbx-Meis1/Prep1.
P. Knoepfler (1999)



This paper is referenced by
10.1161/JAHA.119.012089
Inhibition of Senescence‐Associated Genes Rb1 and Meis2 in Adult Cardiomyocytes Results in Cell Cycle Reentry and Cardiac Repair Post–Myocardial Infarction
Perwez Alam (2019)
Further Characterization Of A Highly Conserved Novel Meis2 Linked Gene And Protein Product
Zachary Williams (2014)
10.32657/10356/50694
Elucidation of the physical and functional interactions between the MEIS1A and the CREB and CRTC transcription factors
Y. M. Looi (2012)
10.1194/jlr.M045922
TG-interacting factor 1 acts as a transcriptional repressor of sterol O-acyltransferase 2[S]
Camilla Pramfalk (2014)
10.1242/dev.174706
MEIS transcription factors in development and disease
Dorothea Schulte (2019)
10.1016/j.devcel.2012.02.009
Congenital asplenia in mice and humans with mutations in a Pbx/Nkx2-5/p15 module.
M. Koss (2012)
10.1002/ajmg.a.40368
De novo missense variants in MEIS2 recapitulate the microdeletion phenotype of cardiac and palate abnormalities, developmental delay, intellectual disability and dysmorphic features
G. Douglas (2018)
10.1016/j.bbagrm.2018.10.005
Myt1 and Myt1l transcription factors limit proliferation in GBM cells by repressing YAP1 expression.
T. Melhuish (2018)
10.1002/ijc.31638
miR-134 targets PDCD7 to reduce E-cadherin expression and enhance oral cancer progression.
Shih-Yuan Peng (2018)
10.1002/jcb.26636
Analysis of transcriptional activity by the Myt1 and Myt1l transcription factors.
Arkadi Manukyan (2018)
10.12691/IJHD-1-1A-3
Cereblon and Its Role in the Treatment of Multiple Myeloma by Lenalidomide or Pomalidomide
Ota Fuchs (2014)
10.1101/gad.318774.118
'Building a perfect body': control of vertebrate organogenesis by PBX-dependent regulatory networks.
Licia Selleri (2019)
10.1074/jbc.M117.802900
IL-10 promoter transactivation by the viral K-RTA protein involves the host-cell transcription factors, specificity proteins 1 and 3
Masanori Miyazawa (2017)
10.1016/j.neuron.2015.10.045
Pbx Regulates Patterning of the Cerebral Cortex in Progenitors and Postmitotic Neurons
Olga Golonzhka (2015)
10.1074/jbc.M113.472183
Nitric Oxide and KLF4 Protein Epigenetically Modify Class II Transactivator to Repress Major Histocompatibility Complex II Expression during Mycobacterium bovis Bacillus Calmette-Guérin Infection*
Devram Sampat Ghorpade (2013)
10.1038/srep16381
New genetic regulators question relevance of abundant yolk protein production in C. elegans
Liesbeth Van Rompay (2015)
10.1371/journal.pone.0042161
Identification of Pluripotent and Adult Stem Cell Genes Unrelated to Cell Cycle and Associated with Poor Prognosis in Multiple Myeloma
Alboukadel Kassambara (2012)
10.1002/dvdy.24016
Biochemistry of the tale transcription factors PREP, MEIS, and PBX in vertebrates
Deneen M Wellik (2014)
10.1002/ajmg.a.36498
Haploinsufficiency of MEIS2 is associated with orofacial clefting and learning disability.
Stefan Johansson (2014)
The role of vertebrate conserved non-coding elements in hindbrain development and evolution
Jm Grice (2016)
10.1177/2045894020908782
Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension
Didem Saygin (2020)
10.1182/blood-2013-02-483792
Redefinition of the human mast cell transcriptome by deep-CAGE sequencing.
E. S. Motakis (2014)
10.1128/MCB.00527-16
Tgif1 and Tgif2 Repress Expression of the RabGAP Evi5l
Anoush E. Anderson (2016)
10.1038/ejhg.2016.164
Genetic and Molecular Analyses indicate independent effects of TGIFs on Nodal and Gli3 in neural tube patterning
Kenichiro Taniguchi (2017)
10.1038/bcj.2017.86
Meis2 as a critical player in MN1-induced leukemia
C K Lai (2017)
10.4049/jimmunol.1502283
The Lupus Susceptibility Gene Pbx1 Regulates the Balance between Follicular Helper T Cell and Regulatory T Cell Differentiation
Seung-Chul Choi (2016)
10.1186/1471-2164-15-910
Transcriptomic portrait of human Mesenchymal Stromal/Stem cells isolated from bone marrow and placenta
Beatriz Roson-Burgo (2014)
10.1016/j.canlet.2018.04.010
The interplay between critical transcription factors and microRNAs in the control of normal and malignant myelopoiesis.
Christiaan J Stavast (2018)
10.1101/gad.320127.118
TGIF transcription factors repress acetyl CoA metabolic gene expression and promote intestinal tumor growth.
Anant Shah (2019)
10.1002/ddr.21223
Genetic findings in obsessive-compulsive disorder connect to brain-derived neutrophic factor and mammalian target of rapamycin pathways: implications for drug development.
Marco A Grados (2014)
10.1002/tox.22160
Identification of time-dependent biomarkers and effects of exposure to volatile organic compounds using high-throughput analysis.
Ji Young Hong (2016)
10.7554/eLife.36144
TALE factors use two distinct functional modes to control an essential zebrafish gene expression program
Franck Ladam (2018)
See more
Semantic Scholar Logo Some data provided by SemanticScholar