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Comment
. 2021 May;53(5):589-590.
doi: 10.1038/s41588-021-00817-y.

Targeting ZNF410 as a potential β-hemoglobinopathy therapy

Laxminath Tumburu  1 , Swee Lay Thein  2
Affiliations
Comment

Targeting ZNF410 as a potential β-hemoglobinopathy therapy

Laxminath Tumburu et al. Nat Genet. 2021 May.

Abstract

The nucleosome remodeling and deacetylase (NuRD) complex is a chromatin modifier and plays a key role in the switch from fetal to adult hemoglobin (Hb). In a new study, Vinjamur et al. identify a fetal Hb repressor, ZNF410, which does not bind directly to the γ-globin promoter but acts via its highly specific regulation of CHD4, a protein subunit of the NuRD complex, presenting a potential approach for therapeutic re-activation of fetal Hb.

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Conflict of interest statement

Competing Interests:

The authors declare no competing financial interests.

Figures

Fig. 1:
Fig. 1:. ZNF410 transactivation of CHD4 by 27 evolutionary conserved DNA-binding motifs.
The 5 zinc-fingers (ZFs) of ZNF410 encoded in exons 6–9 regulate CHD4 expression though occupation of CHD4 chromatin clustered around 2 sites: the promoter and −6 kb enhancer, with evolutionarily conserved 27 motifs. ZNF410 loss by CRISPR/Cas9-based genome editing disrupted this chromatin occupancy resulting in the decreased expression of CHD4, and elevation of fetal hemoglobin without affecting erythropoiesis and cell fitness.
See this image and copyright information in PMC

Comment on

  • ZNF410 represses fetal globin by singular control of CHD4.
    Vinjamur DS, Yao Q, Cole MA, McGuckin C, Ren C, Zeng J, Hossain M, Luk K, Wolfe SA, Pinello L, Bauer DE. Vinjamur DS, et al. Nat Genet. 2021 May;53(5):719-728. doi: 10.1038/s41588-021-00843-w. Epub 2021 Apr 15. Nat Genet. 2021. PMID: 33859416 Free PMC article.

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