TITLE

Widespread Alu repeat-driven expansion of consensus DR2 retinoic acid response elements during primate evolution

AUTHOR(S)
Laperriere, David; Tian-Tian Wang; White, John H; Mader, Sylvie
PUB. DATE
January 2007
SOURCE
BMC Genomics;2007, Vol. 8, p23
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Nuclear receptors are hormone-regulated transcription factors whose signaling controls numerous aspects of development and physiology. Many receptors recognize DNA hormone response elements formed by direct repeats of RGKTCA motifs separated by 1 to 5 bp (DR1-DR5). Although many known such response elements are conserved in the mouse and human genomes, it is unclear to which extent transcriptional regulation by nuclear receptors has evolved specifically in primates. Results: We have mapped the positions of all consensus DR-type hormone response elements in the human genome, and found that DR2 motifs, recognized by retinoic acid receptors (RARs), are heavily overrepresented (108,582 elements). 90% of these are present in Alu repeats, which also contain lesser numbers of other consensus DRs, including 50% of consensus DR4 motifs. Few DR2s are in potentially mobile AluY elements and the vast majority are also present in chimp and macaque. 95.5% of Alu-DR2s are distributed throughout subclasses of AluS repeats, and arose largely through deamination of a methylated CpG dinucleotide in a non-consensus motif present in AluS sequences. We find that Alu-DR2 motifs are located adjacent to numerous known retinoic acid target genes, and show by chromatin immunoprecipitation assays in squamous carcinoma cells that several of these elements recruit RARs in vivo. These findings are supported by ChIP-on-chip data from retinoic acid-treated HL60 cells revealing RAR binding to several Alu-DR2 motifs. Conclusion: These data provide strong support for the notion that Alu-mediated expansion of DR elements contributed to the evolution of gene regulation by RARs and other nuclear receptors in primates and humans.
ACCESSION #
28858762

 

Related Articles

  • Transcriptional regulation of cellular transformation. Salomoni, Paolo; Pandolfi, Pier Paolo // Nature Medicine;Jul2000, Vol. 6 Issue 7, p742 

    Discusses mechanisms by which chimeric transcription factors can lead to cellular transformation. Identification of nuclear hormone receptor superfamily members; Chromosomal translocations in patients with acute promyelocytic leukemia (APL); Association of retinoic acid receptor proteins with APL.

  • Evolution of gene regulation–on the road towards computational inferences. Fuellen, Georg // Briefings in Bioinformatics;Mar2011, Vol. 12 Issue 2, p122 

    If fragments of DNA are transcribed (expressed), they deserve to be called (parts of) a gene. Whether transcription takes place depends on the ‘gene regulatory network’. This network is defined as the complex interplay of the sequence, biochemical modifications and structure of the...

  • Evolution of the hepcidin gene in primates. Segat, Ludovica; Pontillo, Alessandra; Milanese, Michele; Tossi, Alessandro; Crovella, Sergio // BMC Genomics;2008, Vol. 9, Special section p1 

    Background: Hepcidin/LEAP-1 is an iron regulatory hormone originally identified as an antimicrobial peptide. As part of a systematic analysis of the evolution of host defense peptides in primates, we have sequenced the orthologous gene from 14 species of non-human primates. Results: The sequence...

  • The MN1-TEL myeloid leukemia-associated fusion protein has a dominant-negative effect on RAR-RXR-mediated transcription. van Wely, K. H. M.; Meester-Smoor, M. A.; Janssen, M. J. F. W.; Aarnoudse, A.-J.; Grosveld, G. C.; Zwarthoff, E. C. // Oncogene;8/23/2007, Vol. 26 Issue 39, p5733 

    The translocation t(12;22)(p13;q11) creates an MN1-TEL fusion gene leading to acute myeloid leukemia. MN1 is a transcription coactivator of the retinoic acid and vitamin D receptors, and TEL (ETV6) is a member of the E26-transformation-specific family of transcription factors. In MN1-TEL, the...

  • Cloning and characterization of human PREB; a gene that maps to a genomic region associated with trisomy 2p syndrome. Clelland, Catherine L. Taylor; Levy, Brynn; McKie, Judith M.; Duncan, Alessandra M. V.; Hirschhorn, Kurt; Bancroft, Carter // Mammalian Genome;Aug2000, Vol. 11 Issue 8, p675 

    We have isolated the human homolog of a novel rodent gene that may be involved in the regulation of pituitary gene transcription. The human PREB gene encodes a predicted protein of 417 amino acids, exhibiting several sequences characteristic of the WD-motif protein family. PREB transcripts were...

  • A census of human transcription factors: function, expression and evolution. Vaquerizas, Juan M.; Kummerfeld, Sarah K.; Teichmann, Sarah A.; Luscombe, Nicholas M. // Nature Reviews Genetics;Apr2009, Vol. 10 Issue 4, p252 

    Transcription factors are key cellular components that control gene expression: their activities determine how cells function and respond to the environment. Currently, there is great interest in research into human transcriptional regulation. However, surprisingly little is known about these...

  • Lessons from the modular organization of the transcriptional regulatory network of Bacillus subtilis. Freyre-González, Julio A.; Manjarrez-Casas, Alejandra M.; Merino, Enrique; Martinez-Nuñez, Mario; Perez-Rueda, Ernesto; Gutiérrez-Ríos, Rosa-María // BMC Systems Biology;2013, Vol. 7 Issue 1, p1 

    Background The regulation of gene expression at the transcriptional level is a fundamental process in prokaryotes. Among the different kind of mechanisms modulating gene transcription, the one based on DNA binding transcription factors, is the most extensively studied and the results, for a...

  • In Brief.  // Nature Reviews Genetics;Jul2009, Vol. 10 Issue 7, p427 

    The article offers news briefs related to medical research. Patients with Cornelia de Lange syndrome have found to have a transcriptional dysregulation that correlates with phenotypic severity wherein the cohesin could function as a transcription factor. The DNA binding specificity of some...

  • Selective Constraints in Experimentally Defined Primate Regulatory Regions. Gaffney, Daniel J.; Blekhman, Ran; Majewski, Jacek // PLoS Genetics;Aug2008, Vol. 4 Issue 8, p1 

    Changes in gene regulation may be important in evolution. However, the evolutionary properties of regulatory mutations are currently poorly understood. This is partly the result of an incomplete annotation of functional regulatory DNA in many species. For example, transcription factor binding...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics