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Blood, 6 August 2009, Vol. 114, No. 6, pp. 1254-1262. Prepublished online as a Blood First Edition Paper on June 15, 2009; DOI 10.1182/blood-2009-03-210146. This Article Full Text Full Text (PDF) Supplemental Methods, Table, and Figures All Versions of this Article: blood-2009-03-210146v1 114/6/1254    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Wahlberg, K. Articles by Best, S. PubMed PubMed Citation Articles by Wahlberg, K. Articles by Best, S. Related Collections Red Cells, Iron, and Erythropoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS, IRON, AND ERYTHROPOIESIS The HBS1L-MYB intergenic interval associated with elevated HbF levels shows characteristics of a distal regulatory region in erythroid cells Karin Wahlberg1, Jie Jiang1, Helen Rooks1, Kiran Jawaid1, Fumihiko Matsuda2,3, Masao Yamaguchi2,3, Mark Lathrop3, Swee Lay Thein1,4,*, and Steve Best1,* 1 Division of Gene and Cell Based Therapy, King's College London School of Medicine, London, United Kingdom; 2 Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Yoshida, Japan; 3 Centre National de Génotypage, Institut Génomique, Commissariat a l'Energie Atomique, Evry, France; and 4 Department of Haematological Medicine, King's College Hospital, London, United Kingdom HBS1L-MYB intergenic polymorphism (HMIP) on chromosome 6q23 is associated with elevated fetal hemoglobin levels and has pleiotropic effects on several hematologic parameters. To investigate potential regulatory activity in the region, we have measured sensitivity of the sequences to DNase I cleavage that identified 3 tissue-specific DNase I hypersensitive sites in the core intergenic interval. Chromatin immunoprecipitation with microarray (ChIP-chip) analysis showed strong histone acetylation in a defined interval of 65 kb corresponding to the core HBS1L-MYB intergenic region in primary human erythroid cells but not in non–MYB-expressing HeLa cells. ChIP-chip analysis also identified several potential cis-regulatory elements as strong GATA-1 signals that coincided with the DNase I hypersensitive sites present in MYB-expressing erythroid cells. We suggest that HMIP contains regulatory sequences that could be important in hematopoiesis by controlling MYB expression. This study provides the functional link between genetic association of HMIP with control of fetal hemoglobin and other hematologic parameters. We also present a large-scale analysis of histone acetylation as well as RNA polymerase II and GATA-1 interactions on chromosome 6q, and and β globin gene loci. The data suggest that GATA-1 regulates numerous genes of various functions on chromosome 6q. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. L. Thein, S. Menzel, M. Lathrop, and C. Garner Control of fetal hemoglobin: new insights emerging from genomics and clinical implications Hum. Mol. Genet., October 15, 2009; 18(R2): R216 - R223. [Abstract] [Full Text] [PDF]

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