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Publications of the Week

ZNF410 Represses Fetal Globin by Singular Control of CHD4

By May 10, 2021May 17th, 2021No Comments

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This week we profile a recent publication in Nature Genetics from Dr. Divya Vinjamur
(pictured, far right) in the laboratory of Dr. Daniel Bauer (center back).

Can you provide a brief overview of your lab’s current research focus?

Our lab is interested in understanding how our genome encodes blood cell potential, how this can go wrong in disease, and how rational treatment strategies could intervene. We focus on using genome editing technologies to perturb the genome both for discovery and as therapy.

What is the significance of the findings in this publication?

In this project, we performed a CRISPR screen to identify transcription factors that silence fetal hemoglobin (HbF) in adult red blood cells. We discovered ZNF410 to be a novel transcriptional regulator of HbF. Remarkably we observed that ZNF410 is a DNA-binding factor with remarkably only a single direct target in the genome. The target is CHD4, which has 27 binding sites for ZNF410 within its promoter and upstream enhancer elements (unparalleled clusters genome-wide).

What are the next steps for this research?

We would like to understand how ZNF410 binds and activates CHD4 via these bizarre clustered motifs, investigate the biological roles of ZNF410 in human and non-human contexts, and explore therapeutic targeting of ZNF410. This is part of a broader goal to develop rational therapeutic strategies that could scale to the massive global unmet need of hemoglobin disorders like sickle cell disease and thalassemia.

This research was funded by:

NIH/NHLBI and Burroughs Wellcome Fund.

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