Identification of the transcription factor MAZ as a regulator of erythropoiesis

Darya Deen, Deborah E Daniels, Ivan Ferrer-Vicens, Daniel C J Ferguson, Jan Frayne, Douglas Vernimmen*, et al.

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Erythropoiesis requires a combination of ubiquitous and tissue-specific transcription factors (TFs). Here, through DNA affinity purification followed by mass spectrometry, we have identified the widely expressed protein MAZ (Myc-associated zinc finger) as a TF that binds to the promoter of the erythroid-specific human α-globin gene. Genome-wide mapping in primary human erythroid cells revealed that MAZ also occupies active promoters as well as GATA1-bound enhancer elements of key erythroid genes. Consistent with an important role during erythropoiesis, knockdown of MAZ reduces α-globin expression in K562 cells and impairs differentiation in primary human erythroid cells. Genetic variants in the MAZ locus are associated with changes in clinically important human erythroid traits. Taken together, these findings reveal the zinc-finger TF MAZ to be a previously unrecognized regulator of the erythroid differentiation program.
Original languageEnglish
Pages (from-to)3002-3015
Number of pages14
JournalBlood Advances
Volume5
Issue number15
Early online date5 Aug 2021
DOIs
Publication statusPublished - 10 Aug 2021

Bibliographical note

Funding Information:
This work was supported by a University of Edinburgh Chancellor’s Fellowship to D.V. and Institute Strategic Grant funding to the Roslin Institute from the Biotechnology and Biological Sciences Research Council (BB/J004235/1 and BB/P013732/1). D.D. is supported by Roslin Institute core funding to D.V. D.G. was supported by the Medical Research Council (United Kingdom) and INSERM (France).

Publisher Copyright:
© 2021 by The American Society of Hematology

Keywords

  • binding (molecular function)
  • dna
  • erythroid cells
  • erythropoiesis
  • genes
  • globins
  • mass spectrometry
  • oncogenes
  • transcription factor
  • chromatography
  • affinity

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