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 language | English |
|---|---|
| Pages (from-to) | 3002-3015 |
| Number of pages | 14 |
| Journal | Blood Advances |
| Volume | 5 |
| Issue number | 15 |
| Early online date | 5 Aug 2021 |
| DOIs | |
| Publication status | Published - 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