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Identification of the transcription factor MAZ as a regulator of erythropoiesis
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.
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“The top 10 TF binding sites with the highest methylation increase in Tet2-KO relative to WT upon IL1β stimulation in CMPs included GATA1, TAL1, and MAZ which promote erythropoiesis (Fig. 4c)35–37.”
From Clonal hematopoiesis related TET2 loss-of-function impedes IL1β-mediated epigenetic reprogramming in hematopoietic stem and progenitor cells (2023) · cites this paper as [36]
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JASPAR 2020: update of the open-access database of transcription factor binding profiles
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Cited by
McClatchy, J., Strogantsev, R., Wolfe, E., Lin, H. Y., Mohammadhosseini, M., Davis, B. A., Eden, C., Goldman, D., Fleming, W. H., Conley, P., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43697-y · Cited by 95
Metadata
- Authors
- Deen, D., Butter, F., Daniels, D. E., Ferrer-Vicens, I., Ferguson, D. C. J., Holland, M. L., Samara, V., Sloane-Stanley, J. A., Ayyub, H., Mann, M., Frayne, J., Garrick, D., & Vernimmen, D.
- Venue
- Blood Advances
- Publisher
- American Society of Hematology
- Published
- 2021-08-05
- Volume
- 5
- Issue
- 15
- Pages
- 3002-3015
- ISSN
- 2473-9529
- 2473-9537
- Cited by
- 15
- References
- 4
- Language
- en
- Update notices
- erratum (2022-03-16)
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