Differential genomic targeting of the transcription factor TAL1 in alternate haematopoietic lineages

TAL1/SCL is a master regulator of haematopoiesis whose expression promotes opposite outcomes depending on the cell type: differentiation in the erythroid lineage or oncogenesis in the T‐cell lineage. Here, we used a combination of ChIP sequencing and gene expression profiling to compare the function of TAL1 in normal erythroid and leukaemic T cells. Analysis of the genome‐wide binding properties of TAL1 in these two haematopoietic lineages revealed new insight into the mechanism by which transcription factors select their binding sites in alternate lineages. Our study shows limited overlap in the TAL1‐binding profile between the two cell types with an unexpected preference for ETS and RUNX motifs adjacent to E‐boxes in the T‐cell lineage. Furthermore, we show that TAL1 interacts with RUNX1 and ETS1, and that these transcription factors are critically required for TAL1 binding to genes that modulate T‐cell differentiation. Thus, our findings highlight a critical role of the cellular environment in modulating transcription factor binding, and provide insight into the mechanism by which TAL1 inhibits differentiation leading to oncogenesis in the T‐cell lineage.

[1]  G. Bornkamm,et al.  Characterization of EBV‐genome negative “null” and “T” cell lines derived from children with acute lymphoblastic leukemia and leukemic transformed non‐Hodgkin lymphoma , 1977, International journal of cancer.

[2]  A. de Klein,et al.  High expression of ets-1 gene in human thymocytes and immature T leukemic cells. , 1988, Leukemia.

[3]  W. Paul,et al.  Activation events during thymic selection , 1992, The Journal of experimental medicine.

[4]  R. Kingston,et al.  Preferred sequences for DNA recognition by the TAL1 helix-loop-helix proteins , 1994, Molecular and cellular biology.

[5]  N. Muthusamy,et al.  Defective activation and survival of T cells lacking the Ets-1 transcription factor , 1995, Nature.

[6]  J. Leiden,et al.  Transcription factor GATA-3 is required for development of the T-cell lineage , 1996, Nature.

[7]  P. Leder,et al.  Tal‐1 induces T cell acute lymphoblastic leukemia accelerated by casein kinase IIalpha. , 1996, The EMBO journal.

[8]  C. Croce,et al.  Advances in Brief T-Cell . . directed TAL-1 Expression Induces T-Cell Malignancies in Transgenic Mice ' , 2006 .

[9]  T. Rabbitts,et al.  The LIM‐only protein Lmo2 is a bridging molecule assembling an erythroid, DNA‐binding complex which includes the TAL1, E47, GATA‐1 and Ldb1/NLI proteins , 1997, The EMBO journal.

[10]  B. Morgan,et al.  Aiolos, a lymphoid restricted transcription factor that interacts with Ikaros to regulate lymphocyte differentiation , 1997, The EMBO journal.

[11]  A. Cumano,et al.  Sox‐4 facilitates thymocyte differentiation , 1997, European journal of immunology.

[12]  M. Wigler,et al.  PTEN, a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer , 1997, Science.

[13]  M Chilosi,et al.  Differential expression of cyclin-dependent kinase 6 in cortical thymocytes and T-cell lymphoblastic lymphoma/leukemia. , 1998, The American journal of pathology.

[14]  O. Yoshie,et al.  TAL1 and LIM-Only Proteins Synergistically Induce Retinaldehyde Dehydrogenase 2 Expression in T-Cell Acute Lymphoblastic Leukemia by Acting as Cofactors for GATA3 , 1998, Molecular and Cellular Biology.

[15]  E. Macintyre,et al.  Helix-loop-helix (E2-5, HEB, TAL1 and Id1) protein interaction with the TCRalphadelta enhancers. , 1998, International immunology.

[16]  Y Fujiwara,et al.  Different sequence requirements for expression in erythroid and megakaryocytic cells within a regulatory element upstream of the GATA-1 gene. , 1999, Development.

[17]  A. Green,et al.  The SCL gene: from case report to critical hematopoietic regulator. , 1999, Blood.

[18]  T. Taniguchi,et al.  Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. , 2000, Science.

[19]  A. Kimchi,et al.  Death-Associated Protein Kinase-Related Protein 1, a Novel Serine/Threonine Kinase Involved in Apoptosis , 2000, Molecular and Cellular Biology.

[20]  R. Tibshirani,et al.  Significance analysis of microarrays applied to the ionizing radiation response , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[21]  W. Dai,et al.  Plk3 Functionally Links DNA Damage to Cell Cycle Arrest and Apoptosis at Least in Part via the p53 Pathway* , 2001, The Journal of Biological Chemistry.

[22]  E. Green,et al.  Mutational and functional analyses reveal that ST7 is a highly conserved tumor-suppressor gene on human chromosome 7q31 , 2001, Nature Genetics.

[23]  T. Hoang,et al.  functional interaction with Sp 1 expression in hematopoietic cells through c-kit The SCL-complex regulates , 2002 .

[24]  C. Murre,et al.  E protein function in lymphocyte development. , 2002, Annual review of immunology.

[25]  E. Lander,et al.  Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. , 2002, Cancer cell.

[26]  Long-Sheng Chang,et al.  Identification of a TAL1 Target Gene Reveals a Positive Role for the LIM Domain-Binding Protein Ldb1 in Erythroid Gene Expression and Differentiation , 2003, Molecular and Cellular Biology.

[27]  Rafael A Irizarry,et al.  Exploration, normalization, and summaries of high density oligonucleotide array probe level data. , 2003, Biostatistics.

[28]  Daniel G. Tenen,et al.  Disruption of differentiation in human cancer: AML shows the way , 2003, Nature Reviews Cancer.

[29]  T. Hoang,et al.  SCL: from the origin of hematopoiesis to stem cells and leukemia. , 2004, Experimental hematology.

[30]  Kristina Hanspers,et al.  Gene expression profiles during human CD4+ T cell differentiation. , 2004, International immunology.

[31]  T. Speed,et al.  GOstat: find statistically overrepresented Gene Ontologies within a group of genes. , 2004, Bioinformatics.

[32]  Peter C. Hollenhorst,et al.  Expression profiles frame the promoter specificity dilemma of the ETS family of transcription factors. , 2004, Nucleic acids research.

[33]  T. Hoang,et al.  SCL Assembles a Multifactorial Complex That Determines Glycophorin A Expression , 2004, Molecular and Cellular Biology.

[34]  Laurent Kiger,et al.  Ex vivo generation of fully mature human red blood cells from hematopoietic stem cells , 2005, Nature Biotechnology.

[35]  Karen Blyth,et al.  The runx genes: gain or loss of function in cancer , 2005, Nature Reviews Cancer.

[36]  Pablo Tamayo,et al.  Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[37]  S. Brandt,et al.  Tal1/SCL Binding to Pericentromeric DNA Represses Transcription* , 2005, Journal of Biological Chemistry.

[38]  L. Rénia,et al.  SCL/TAL1 expression level regulates human hematopoietic stem cell self-renewal and engraftment. , 2005, Blood.

[39]  F. Sánchez‐Madrid,et al.  CD69 is an immunoregulatory molecule induced following activation. , 2005, Trends in immunology.

[40]  M. Kelliher,et al.  NFKB1 is a direct target of the TAL1 oncoprotein in human T leukemia cells. , 2006, Cancer research.

[41]  Isaac Engel,et al.  Gene expression patterns define novel roles for E47 in cell cycle progression, cytokine-mediated signaling, and T lineage development. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[42]  P. Romeo,et al.  Low SCL / TAL 1 expression reveals its major role in adult hematopoietic myeloid progenitors and stem cells , 2006 .

[43]  G. Gilkeson,et al.  ETS transcription factors and regulation of immunity , 2006, Archivum Immunologiae et Therapiae Experimentalis.

[44]  Adam A. Margolin,et al.  Transcriptional regulatory networks downstream of TAL1/SCL in T-cell acute lymphoblastic leukemia. , 2005, Blood.

[45]  P. Hinds,et al.  Beyond the cell cycle: A new role for Cdk6 in differentiation , 2006, Journal of cellular biochemistry.

[46]  P. Romeo,et al.  Low SCL/TAL1 expression reveals its major role in adult hematopoietic myeloid progenitors and stem cells. , 2006, Blood.

[47]  Michele K. Anderson.  At the crossroads: diverse roles of early thymocyte transcriptional regulators , 2006, Immunological reviews.

[48]  Yoshiaki Ito,et al.  Pim-1 kinase phosphorylates RUNX family transcription factors and enhances their activity , 2006, BMC Cell Biology.

[49]  Ruedi Aebersold,et al.  Activator-mediated recruitment of the MLL2 methyltransferase complex to the beta-globin locus. , 2007, Molecular cell.

[50]  Quantitative Proteomics by Mass Spectrometry – Methods in Molecular Biology Series. By Salvatore Sechi (Ed.) , 2007 .

[51]  A. Look,et al.  Mechanisms of transcription factor deregulation in lymphoid cell transformation , 2007, Oncogene.

[52]  Chunhui Hou,et al.  A positive role for NLI/Ldb1 in long-range beta-globin locus control region function. , 2007, Molecular cell.

[53]  A. Ferrando,et al.  The role of the PTEN/AKT Pathway in NOTCH1-induced leukemia , 2008, Cell cycle.

[54]  F. Tashiro,et al.  p53 target gene AEN is a nuclear exonuclease required for p53-dependent apoptosis , 2008, Oncogene.

[55]  E. Raetz,et al.  Molecular pathogenesis of T-cell leukaemia and lymphoma , 2008, Nature Reviews Immunology.

[56]  J. Kaye,et al.  Development of all CD4 T lineages requires nuclear factor TOX. , 2008, The Journal of experimental medicine.

[57]  Ruth Nussinov,et al.  How do transcription factors select specific binding sites in the genome? , 2009, Nature Structural &Molecular Biology.

[58]  B. Göttgens,et al.  Expression of the leukemia oncogene Lmo2 is controlled by an array of tissue-specific elements dispersed over 100 kb and bound by Tal1/Lmo2, Ets, and Gata factors. , 2009, Blood.

[59]  Francesca Chiaromonte,et al.  Erythroid GATA 1 function revealed by genome-wide analysis of transcription factor occupancy , histone modifications , and mRNA expression , 2009 .

[60]  C. Palii,et al.  Dual role for the methyltransferase G9a in the maintenance of β-globin gene transcription in adult erythroid cells , 2009, Proceedings of the National Academy of Sciences.

[61]  Barbara J. Graves,et al.  DNA Specificity Determinants Associate with Distinct Transcription Factor Functions , 2009, PLoS genetics.

[62]  Henriette O'Geen,et al.  Discovering hematopoietic mechanisms through genome-wide analysis of GATA factor chromatin occupancy. , 2009, Molecular cell.

[63]  A. Ma,et al.  A20 takes on tumors: tumor suppression by an ubiquitin-editing enzyme , 2009, The Journal of experimental medicine.

[64]  R. Hardison,et al.  SCL and associated proteins distinguish active from repressive GATA transcription factor complexes. , 2008, Blood.

[65]  L. Chin,et al.  High frequency of PTEN, PI3K, and AKT abnormalities in T-cell acute lymphoblastic leukemia. , 2009, Blood.

[66]  Mark A. Dawson,et al.  The transcriptional program controlled by the stem cell leukemia gene Scl/Tal1 during early embryonic hematopoietic development. , 2009, Blood.

[67]  G. Hu,et al.  A requirement for cyclin-dependent kinase 6 in thymocyte development and tumorigenesis. , 2009, Cancer research.

[68]  F. Sablitzky,et al.  Adult hematopoietic stem and progenitor cells require either Lyl1 or Scl for survival. , 2009, Cell stem cell.

[69]  H. Bujard,et al.  Expression of CD226 Antagonizes Apoptotic Cell Death in Murine Thymocytes1 , 2009, The Journal of Immunology.

[70]  Christine Steinhoff,et al.  The genome-wide dynamics of the binding of Ldb1 complexes during erythroid differentiation. , 2010, Genes & development.

[71]  W. Ouwehand,et al.  Combinatorial transcriptional control in blood stem/progenitor cells: genome-wide analysis of ten major transcriptional regulators. , 2010, Cell stem cell.

[72]  W. L. Ruzzo,et al.  Genome-wide MyoD binding in skeletal muscle cells: a potential for broad cellular reprogramming. , 2010, Developmental cell.

[73]  A. Haman,et al.  Scl regulates the quiescence and the long-term competence of hematopoietic stem cells. , 2009, Blood.

[74]  Shamit Soneji,et al.  Genome-wide identification of TAL1's functional targets: insights into its mechanisms of action in primary erythroid cells. , 2010, Genome research.