Transcription factors: specific DNA binding and specific gene regulation.

Specific recognition of cis-regulatory regions is essential for correct gene regulation in response to developmental and environmental signals. Such DNA sequences are recognized by transcription factors (TFs) that recruit the transcriptional machinery. Achievement of specific sequence recognition is not a trivial problem; many TFs recognize similar consensus DNA-binding sites and a genome can harbor thousands of consensus or near-consensus sequences, both functional and nonfunctional. Although genomic technologies have provided large-scale snapshots of TF binding, a full understanding of the mechanistic and quantitative details of specific recognition in the context of gene regulation is lacking. Here, we explore the various ways in which TFs recognizing similar consensus sites distinguish their own targets from a large number of other sequences to ensure specific cellular responses.

[1]  L. Mirny,et al.  Different gene regulation strategies revealed by analysis of binding motifs. , 2009, Trends in genetics : TIG.

[2]  Alexandre V Morozov,et al.  Chromatin-dependent transcription factor accessibility rather than nucleosome remodeling predominates during global transcriptional restructuring in Saccharomyces cerevisiae. , 2009, Molecular biology of the cell.

[3]  P. J. Bhat,et al.  Integration of Global Signaling Pathways, cAMP-PKA, MAPK and TOR in the Regulation of FLO11 , 2008, PloS one.

[4]  Albin Sandelin,et al.  The genome landscape of ERα- and ERβ-binding DNA regions , 2008, Proceedings of the National Academy of Sciences.

[5]  Sarah A. Teichmann,et al.  Genomic repertoires of DNA-binding transcription factors across the tree of life , 2010, Nucleic acids research.

[6]  M. Merika,et al.  The role of HMG I(Y) in the assembly and function of the IFN‐β enhanceosome , 1999, The EMBO journal.

[7]  S. Burley,et al.  Binding of the winged‐helix transcription factor HNF3 to a linker histone site on the nucleosome , 1998, The EMBO journal.

[8]  P. V. von Hippel,et al.  Nonspecific DNA binding of genome-regulating proteins as a biological control mechanism: measurement of DNA-bound Escherichia coli lac repressor in vivo. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Ralf J. Sommer,et al.  The evolution of signalling pathways in animal development , 2003, Nature Reviews Genetics.

[10]  John Reinitz,et al.  Bicoid cooperative DNA binding is critical for embryonic patterning in Drosophila. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[11]  N. D. Clarke,et al.  Integrative model of genomic factors for determining binding site selection by estrogen receptor-α , 2010, Molecular systems biology.

[12]  K. Zaret,et al.  An active tissue-specific enhancer and bound transcription factors existing in a precisely positioned nucleosomal array , 1993, Cell.

[13]  R. Veitia,et al.  A sigmoidal transcriptional response: cooperativity, synergy and dosage effects , 2003, Biological reviews of the Cambridge Philosophical Society.

[14]  Syr-yaung Lin,et al.  The general affinity of lac repressor for E. coli DNA: Implications for gene regulation in procaryotes and eucaryotes , 1975, Cell.

[15]  H. Gronemeyer,et al.  Transcription activation by estrogen and progesterone receptors. , 1991, Annual review of genetics.

[16]  T. Furey.  ChIP – seq and beyond : new and improved methodologies to detect and characterize protein – DNA interactions , 2012 .

[17]  P. Fraser,et al.  Transcription factories: genetic programming in three dimensions. , 2012, Current opinion in genetics & development.

[18]  K. Zaret,et al.  GATA transcription factors as potentiators of gut endoderm differentiation. , 1998, Development.

[19]  Juan M. Vaquerizas,et al.  Multiplexed massively parallel SELEX for characterization of human transcription factor binding specificities. , 2010, Genome research.

[20]  J. Greer,et al.  Maintenance of functional equivalence during paralogous Hox gene evolution , 2000, Nature.

[21]  Daniel E. Newburger,et al.  Diversity and Complexity in DNA Recognition by Transcription Factors , 2009, Science.

[22]  Victor X Jin,et al.  E2F in vivo binding specificity: comparison of consensus versus nonconsensus binding sites. , 2008, Genome research.

[23]  R. Veitia,et al.  Protein–Protein and Protein–DNA Dosage Balance and Differential Paralog Transcription Factor Retention in Polyploids , 2011, Front. Plant Sci..

[24]  William Stafford Noble,et al.  Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors , 2012, Genome research.

[25]  M. Freeling,et al.  Dose–Sensitivity, Conserved Non-Coding Sequences, and Duplicate Gene Retention Through Multiple Tetraploidies in the Grasses , 2011, Front. Plant Sci..

[26]  S. Potter,et al.  Functional specificity of the Hoxa13 homeobox. , 2001, Development.

[27]  R. Marmorstein,et al.  Structural basis for DNA recognition by FoxO1 and its regulation by posttranslational modification. , 2008, Structure.

[28]  M. Strazzabosco.  Foxa1 and Foxa2 regulate bile duct development in mice. , 2010, Journal of hepatology.

[29]  C C Adams,et al.  Binding of disparate transcriptional activators to nucleosomal DNA is inherently cooperative , 1995, Molecular and cellular biology.

[30]  Diego Miranda-Saavedra,et al.  Distinct transcriptional regulatory modules underlie STAT3’s cell type-independent and cell type-specific functions , 2013, Nucleic acids research.

[31]  K. Umesono,et al.  Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors , 1991, Cell.

[32]  Frédérique Lisacek,et al.  Absolute quantification of transcription factors during cellular differentiation using multiplexed targeted proteomics , 2013, Nature Methods.

[33]  J. Eeckhoute,et al.  Pioneer factors: directing transcriptional regulators within the chromatin environment. , 2011, Trends in genetics : TIG.

[34]  C. Glass,et al.  RXRβ: A coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements , 1991, Cell.

[35]  Hernan G. Garcia,et al.  Supplemental Information The Transcription Factor Titration Effect Dictates Level of Gene Expression , 2014 .

[36]  J. Carroll,et al.  Pioneer transcription factors: establishing competence for gene expression. , 2011, Genes & development.

[37]  J. Stamatoyannopoulos,et al.  Quantitative Models of the Mechanisms That Control Genome-Wide Patterns of Transcription Factor Binding during Early Drosophila Development , 2011, PLoS genetics.

[38]  M. Levine.  Transcriptional Enhancers in Animal Development and Evolution , 2010, Current Biology.

[39]  Kurt Wüthrich,et al.  Homeodomain-DNA recognition , 1994, Cell.

[40]  B. Katzenellenbogen,et al.  Genome-wide dynamics of chromatin binding of estrogen receptors alpha and beta: mutual restriction and competitive site selection. , 2010, Molecular endocrinology.

[41]  Samuel Bottani,et al.  Gene dosage effects: nonlinearities, genetic interactions, and dosage compensation. , 2013, Trends in genetics : TIG.

[42]  James B. Brown,et al.  DNA regions bound at low occupancy by transcription factors do not drive patterned reporter gene expression in Drosophila , 2012, Proceedings of the National Academy of Sciences.

[43]  A. Joerger,et al.  Conservation of DNA-binding specificity and oligomerisation properties within the p53 family , 2009, BMC Genomics.

[44]  Steven J. M. Jones,et al.  Dynamic Remodeling of Individual Nucleosomes Across a Eukaryotic Genome in Response to Transcriptional Perturbation , 2007, PLoS biology.

[45]  Jing Li,et al.  Atypical E2Fs: new players in the E2F transcription factor family. , 2009, Trends in cell biology.

[46]  S. Batzoglou,et al.  Genome-Wide Analysis of Transcription Factor Binding Sites Based on ChIP-Seq Data , 2008, Nature Methods.

[47]  B. Benayoun,et al.  A post-translational modification code for transcription factors: sorting through a sea of signals. , 2009, Trends in cell biology.

[48]  S. Burley,et al.  Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5 , 1993, Nature.

[49]  N. Dostatni,et al.  Bicoid Determines Sharp and Precise Target Gene Expression in the Drosophila Embryo , 2005, Current Biology.

[50]  Aaron Klug,et al.  The discovery of zinc fingers and their development for practical applications in gene regulation and genome manipulation , 2010, Quarterly Reviews of Biophysics.

[51]  M. Biggin.  Animal transcription networks as highly connected, quantitative continua. , 2011, Developmental cell.

[52]  Clifford A. Meyer,et al.  Nucleosome Dynamics Define Transcriptional Enhancers , 2010, Nature Genetics.

[53]  J. Workman,et al.  Stable co‐occupancy of transcription factors and histones at the HIV‐1 enhancer , 1997, The EMBO journal.

[54]  Sandrine Caburet,et al.  Generic binding sites, generic DNA‐binding domains: where does specific promoter recognition come from? , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[55]  S. Tapscott,et al.  Modeling stochastic gene expression: implications for haploinsufficiency. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[56]  D. Thanos,et al.  Stochastic Responses Are Not Left to Pure “Chance” , 2013, Cell.

[57]  Klaus H. Kaestner,et al.  The initiation of liver development is dependent on Foxa transcription factors , 2005, Nature.

[58]  J. R. Coleman,et al.  Hepatic specification of the gut endoderm in vitro: cell signaling and transcriptional control. , 1996, Genes & development.

[59]  J. Elf,et al.  Probing Transcription Factor Dynamics at the Single-Molecule Level in a Living Cell , 2007, Science.

[60]  Allen D. Delaney,et al.  Genome-wide profiles of STAT1 DNA association using chromatin immunoprecipitation and massively parallel sequencing , 2007, Nature Methods.

[61]  M. Carey,et al.  The Enhanceosome and Transcriptional Synergy , 1998, Cell.

[62]  James B. Brown,et al.  Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions , 2009, Genome Biology.

[63]  L. Gold,et al.  Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. , 1990, Science.

[64]  D. W. Knowles,et al.  Transcription Factors Bind Thousands of Active and Inactive Regions in the Drosophila Blastoderm , 2008, PLoS biology.

[65]  Tom Misteli,et al.  Global Nature of Dynamic Protein-Chromatin Interactions In Vivo: Three-Dimensional Genome Scanning and Dynamic Interaction Networks of Chromatin Proteins , 2004, Molecular and Cellular Biology.

[66]  David L Robertson,et al.  Choose your partners: dimerization in eukaryotic transcription factors. , 2008, Trends in biochemical sciences.