Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

85 Scopus Citations
View graph of relations

Author(s)

  • Takeshi Masuda
  • 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

Detail(s)

Original languageEnglish
Pages (from-to)285-289
Journal / PublicationScience
Volume351
Issue number6270
Publication statusPublished - 15 Jan 2016
Externally publishedYes

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.

Citation Format(s)

Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin. / Masuda, Takeshi; Wang, Xin; Maeda, Manami; Canver, Matthew C.; Sher, Falak; Funnell, Alister P.W.; Fisher, Chris; Suciu, Maria; Martyn, Gabriella E.; Norton, Laura J.; Zhu, Catherine; Kurita, Ryo; Nakamura, Yukio; Xu, Jian; Higgs, Douglas R.; Crossley, Merlin; Bauer, Daniel E.; Orkin, Stuart H.; Kharchenko, Peter V.; Maeda, Takahiro.

In: Science, Vol. 351, No. 6270, 15.01.2016, p. 285-289.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal