Show simple item record

dc.contributor.authorXu, Jian
dc.contributor.authorSankaran, Vijay G.
dc.contributor.authorNi, Min
dc.contributor.authorMenne, Tobias F.
dc.contributor.authorPuram, Rishi Venkata
dc.contributor.authorKim, Woojin
dc.contributor.authorOrkin, Stuart H.
dc.date.accessioned2014-07-25T16:33:17Z
dc.date.available2014-07-25T16:33:17Z
dc.date.issued2010-04
dc.date.submitted2010-02
dc.identifier.issn0890-9369
dc.identifier.urihttp://hdl.handle.net/1721.1/88498
dc.description.abstractThe developmental switch from human fetal (γ) to adult (β) hemoglobin represents a clinically important example of developmental gene regulation. The transcription factor BCL11A is a central mediator of γ-globin silencing and hemoglobin switching. Here we determine chromatin occupancy of BCL11A at the human β-globin locus and other genomic regions in vivo by high-resolution chromatin immunoprecipitation (ChIP)–chip analysis. BCL11A binds the upstream locus control region (LCR), ɛ-globin, and the intergenic regions between γ-globin and δ-globin genes. A chromosome conformation capture (3C) assay shows that BCL11A reconfigures the β-globin cluster by modulating chromosomal loop formation. We also show that BCL11A and the HMG-box-containing transcription factor SOX6 interact physically and functionally during erythroid maturation. BCL11A and SOX6 co-occupy the human β-globin cluster along with GATA1, and cooperate in silencing γ-globin transcription in adult human erythroid progenitors. These findings collectively demonstrate that transcriptional silencing of γ-globin genes by BCL11A involves long-range interactions and cooperation with SOX6. Our findings provide insight into the mechanism of BCL11A action and new clues for the developmental gene regulatory programs that function at the β-globin locus.en_US
dc.description.sponsorshipKay Kendall Leukaemia Funden_US
dc.description.sponsorshipHoward Hughes Medical Institute (Investigator)en_US
dc.description.sponsorshipNational Heart, Lung, and Blood Instituteen_US
dc.description.sponsorshipNational Institute of Diabetes and Digestive and Kidney Diseases (U.S.)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.)en_US
dc.description.sponsorshipHelen Hay Whitney Foundation (HHMI fellow)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Medical Scientist Training Program Award)en_US
dc.language.isoen_US
dc.publisherCold Spring Harbor Laboratory Pressen_US
dc.relation.isversionofhttp://dx.doi.org/10.1101/gad.1897310en_US
dc.rightsArticle is available under a Creative Commons license; see publisher’s site for details.en_US
dc.rights.urihttp://creativecommons.org/en_US
dc.sourceCold Spring Harbor Laboratory Pressen_US
dc.titleTranscriptional silencing of γ-globin by BCL11A involves long-range interactions and cooperation with SOX6en_US
dc.typeArticleen_US
dc.identifier.citationXu, J., V. G. Sankaran, M. Ni, T. F. Menne, R. V. Puram, W. Kim, and S. H. Orkin. “Transcriptional Silencing of  γ-Globin by BCL11A Involves Long-Range Interactions and Cooperation with SOX6.” Genes & Development 24, no. 8 (April 15, 2010): 783–798.en_US
dc.contributor.departmentHarvard University--MIT Division of Health Sciences and Technologyen_US
dc.contributor.mitauthorPuram, Rishi Venkataen_US
dc.contributor.mitauthorSankaran, Vijay G.en_US
dc.relation.journalGenes & Developmenten_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsXu, J.; Sankaran, V. G.; Ni, M.; Menne, T. F.; Puram, R. V.; Kim, W.; Orkin, S. H.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-7712-3231
mit.licensePUBLISHER_CCen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record