2. Academic Validation
  3. Human fetal globin gene expression is regulated by LYAR

Human fetal globin gene expression is regulated by LYAR

  • Nucleic Acids Res. 2014 Sep;42(15):9740-52. doi: 10.1093/nar/gku718.
Junyi Ju 1,  Ying Wang 1,  Ronghua Liu 1,  Yichong Zhang 1,  Zhen Xu 1,  Yadong Wang 1,  Yupeng Wu 1,  Ming Liu 1,  Loretta Cerruti 2,  Fengwei Zou 3,  Chi Ma 1,  Ming Fang 4,  Renxiang Tan 1,  Stephen M Jane 5,  Quan Zhao 6
Affiliations

Affiliations

  • 1 The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
  • 2 Department of Medicine, Monash University Central Clinical School, Prahran, VIC 3181, Australia.
  • 3 Department of Chemistry, Northwestern University, Evanston, IL 60208, USA.
  • 4 Institute of Life Sciences, Southeast University, Nanjing 210096, China.
  • 5 Department of Medicine, Monash University Central Clinical School, Prahran, VIC 3181, Australia [email protected].
  • 6 The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China [email protected].
PMID: 25092918 DOI: 10.1093/nar/gku718
Abstract

Human globin gene expression during development is modulated by transcription factors in a stage-dependent manner. However, the mechanisms controlling the process are still largely unknown. In this study, we found that a nuclear protein, LYAR (human homologue of mouse Ly-1 antibody reactive clone) directly interacted with the methyltransferase PRMT5 which triggers the histone H4 Arg3 symmetric dimethylation (H4R3me2s) mark. We found that PRMT5 binding on the proximal γ-promoter was LYAR-dependent. The LYAR DNA-binding motif (GGTTAT) was identified by performing CASTing (cyclic amplification and selection of targets) experiments. Results of EMSA and ChIP assays confirmed that LYAR bound to a DNA region corresponding to the 5'-untranslated region of the γ-globin gene. We also found that LYAR repressed human fetal globin gene expression in both K562 cells and primary human adult erythroid progenitor cells. Thus, these data indicate that LYAR acts as a novel transcription factor that binds the γ-globin gene, and is essential for silencing the γ-globin gene.

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