@article{f77d0c371be84a839f3f7b890ce0cca9,
title = "Gene regulation: Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin",
abstract = "Genes encoding human β-type globin undergo a developmental switch from embryonic to fetal to adult-type expression. Mutations in the adult form cause inherited hemoglobinopathies or globin disorders, including sickle cell disease and thalassemia. Some experimental results have suggested that these diseases could be treated by induction of fetal-type hemoglobin (HbF). However, the mechanisms that repress HbF in adults remain unclear. We found that the LRF/ZBTB7A transcription factor occupies fetal γ-globin genes and maintains the nucleosome density necessary for γ-globin gene silencing in adults, and that LRF confers its repressive activity through a NuRD repressor complex independent of the fetal globin repressor BCL11A. Our study may provide additional opportunities for therapeutic targeting in the treatment of hemoglobinopathies.",
author = "Takeshi Masuda and Xin Wang and Manami Maeda and Canver, {Matthew C.} and Falak Sher and Funnell, {Alister P W} and Chris Fisher and Maria Suciu and Martyn, {Gabriella E.} and Norton, {Laura J.} and Catherine Zhu and Ryo Kurita and Yukio Nakamura and Jian Xu and Higgs, {Douglas R.} and Merlin Crossley and Bauer, {Daniel E.} and Orkin, {Stuart H.} and Kharchenko, {Peter V.} and Takahiro Maeda",
note = "Funding Information: We thank L. Droogmans for advice, as well as A. Rao and J. Kadonaga for continued support. We also thank Y. N. Jan for providing the antibody to Dpn. R.D., B.H., C.C., and E.B. were supported by the Belgian Fonds de la Recherche Scientifique (FNRS). B.D. was supported by the FNRS («Aspirant{"}) and a Belgian American Educational Foundation (BAEF) fellowship. L.V.N. was supported by the Belgian Fund for Research Training in Industry and Agriculture and a BAEF fellowship. E.Co. was supported by a {"}l''Or{\'e}al{"} fellowship, and M.D. was supported by the WBHealth grant (CanDx) from the Walloon Region. F.F. is a ULB Professor. F.F.''s lab was funded by grants from the FNRS and T{\'e}l{\'e}vie, the Interuniversity Attraction Poles (P7/03) program, the Action de Recherche Concert{\'e}e (ARC) (AUWB-2010-2015 ULB-No 7), the WB Health program, the Belgian Fondation contre le Cancer, and the Fonds Gaston Ithier. F.W. was supported by a Charles and Johanna Busch graduate fellowship and the work at Rutgers by a NIH grant (RO1 GM089992) to R.S. V.K. was supported by the ARC (AV.12/17) as well as Brachet and Van Buuren Funds. P.A.L. received financial support from the National Science Foundation (NSF CHE 1212625 and 1507357). The authors declare no conflicts of interest. All sequencing data have been deposited to the Gene Expression Omnibus as series GSE66090. We thank P. Jarolim, D. Dorfman, and other members of BWH Hematology laboratory for help on HPLC analysis; J. Hughes, J. Eglinton, J. Sharp, C. Babbs, K. di Gleria, D. Chen, and P. Schupp for technical support and assistance; E. Lamar for critical reading of the manuscript; and S-U. Lee, H. Yi, Y. Ishikawa and other members of the Maeda lab for help and advice. Supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Predoctoral National Research Service Award for M.D./Ph.D. Fellowship F30DK103359-01A1 (M.C.C.), NIDDK Career Development Award K08DK093705 and Doris Duke Charitable Foundation Innovations in Clinical Research Award 2013137 (D.E.B.), NIH grants P01HL032262 and P30DK049216 (Center of Excellence in Molecular Hematology) (S.H.O.), NIH grant 5K25AG037596 and Ellison Medical Foundation grant AG-NS-0965-12 (P.V.K.), and NIH grants R01 AI084905 and R56 DK105001 and an American Society of Hematology Bridge Program grant (T. Maeda). All reagents described in this manuscript (mouse models, plasmids) are available to the scientific community upon request. Sequencing data are available at the NCBI Gene Expression Omnibus (GEO accession number GSE74977). T. Masuda, M. Maeda, and T. Maeda are contributors to a patent application filed on behalf of Brigham and Women''s Hospital related to therapeutic targeting of LRF/NuRD interaction.",
year = "2016",
month = jan,
day = "15",
doi = "10.1126/science.aad3312",
language = "English (US)",
volume = "351",
pages = "285--289",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6270",
}