Tissue-specific and developmental stage-specific DNA binding by a mammalian SWI/SNF complex associated with human fetal-to-adult globin gene switching Journal Article


Authors: O'Neill, D.; Yang, J.; Erdjument-Bromage, H.; Bornschlegel, K.; Tempst, P.; Bank, A.
Article Title: Tissue-specific and developmental stage-specific DNA binding by a mammalian SWI/SNF complex associated with human fetal-to-adult globin gene switching
Abstract: SWI/SNF complexes in yeast and higher eukaryotes are thought to facilitate gene activation and transcription factor binding by disrupting repressive chromatin structures. Little is known, however, about how these complexes target specific genes for activation. We now have purified a specialized SWI/SNF-related complexes (PYR complex) from murine erythroleukemia (MEL) cell nuclear extract that binds pyrimidine-rich elements at the human and murine β-globin loci. PYR complex DNA-binding activity is restricted to definitive hematopoietic cells and is both DNA sequence- and length-dependent. Mass spectrometric identification of purified peptides and antibody supershift assays indicate that PYR complex contains at least four known mammalian SWI/SNF subunits: BAF57, INI1, BAF60a, and BAF170. PYR complex broadly footprints a 250-bp pyrimidine-rich element between the human fetal and adult β-globin genes. A short intergenic deletion that removes this element from a human globin locus cosmid construct results in delayed human fetal-to-adult globin gene switching in transgenic mice. Taken together, the data suggest that PYR complex may act through this intergenic element to facilitate human fetal-to-adult globin gene switching, presumably by opening the locus in the region of the adult genes to permit the binding of β-globin transcriptional activators.
Keywords: controlled study; dna binding protein; human cell; dna-binding proteins; sequence deletion; nonhuman; animal cell; mouse; mammalia; animals; mice; protein dna binding; tumor cells, cultured; animalia; mus musculus; mice, transgenic; gene activation; transcription regulation; eukaryota; globin gene; murinae; gene switching; chromatin structure; globins; tissue specificity; gene regulation; leukemia, erythroblastic, acute; dna footprinting; hemoglobin a; chromatin remodeling; genes, switch; humans; human; priority journal; article; fetal hemoglobin
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 96
Issue: 2
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 1999-01-01
Start Page: 349
End Page: 354
Language: English
DOI: 10.1073/pnas.96.2.349
PUBMED: 9892636
PROVIDER: scopus
PMCID: PMC15139
DOI/URL:
Notes: Article -- Export Date: 16 August 2016 -- Source: Scopus
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  1. Paul J Tempst
    323 Tempst