Gene regulation: Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin

Takeshi Masuda, Xin Wang, Manami Maeda, Matthew C. Canver, Falak Sher, Alister P W Funnell, Chris Fisher, Maria Suciu, Gabriella E. Martyn, Laura J. Norton, Catherine Zhu, Ryo Kurita, Yukio Nakamura, Jian Xu, Douglas R. Higgs, Merlin Crossley, Daniel E. Bauer, Stuart H. Orkin, Peter V. Kharchenko, Takahiro Maeda

Research output: Contribution to journalArticle

94 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)285-289
Number of pages5
JournalScience
Volume351
Issue number6270
DOIs
StatePublished - Jan 15 2016

ASJC Scopus subject areas

  • General
  • Medicine(all)

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    Masuda, T., Wang, X., Maeda, M., Canver, M. C., Sher, F., Funnell, A. P. W., Fisher, C., Suciu, M., Martyn, G. E., Norton, L. J., Zhu, C., Kurita, R., Nakamura, Y., Xu, J., Higgs, D. R., Crossley, M., Bauer, D. E., Orkin, S. H., Kharchenko, P. V., & Maeda, T. (2016). Gene regulation: Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin. Science, 351(6270), 285-289. https://doi.org/10.1126/science.aad3312