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During the essential and conserved process of zygotic genome activation (ZGA), chromatin accessibility must increase to promote transcription. Drosophila is a well-established model for defining mechanisms that drive ZGA. Zelda (ZLD) is a key pioneer transcription factor (TF) that promotes ZGA in the Drosophila embryo. However, many genomic loci that contain GA-rich motifs become accessible during ZGA independent of ZLD. Therefore, we hypothesized that other early TFs that function with ZLD have not yet been identified, especially those that are capable of binding to GA-rich motifs such as chromatin-linked adaptor for male-specific lethal (MSL) proteins (CLAMP). Here, we demonstrate that Drosophila embryonic development requires maternal CLAMP to (1) activate zygotic transcription; (2) increase chromatin accessibility at promoters of specific genes that often encode other essential TFs; and (3) enhance chromatin accessibility and facilitate ZLD occupancy at a subset of key embryonic promoters. Thus, CLAMP functions as a pioneer factor that plays a targeted yet essential role in ZGA.
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Randomly incorporated genomic N6 ‐methyldeoxyadenosine delays zygotic transcription initiation in a cnidarian
Abstract N6‐methyldeoxyadenosine (6mA) is a chemical alteration of DNA, observed across all realms of life. Although the functions of 6mA are well understood in bacteria and protists, its roles in animal genomes have been controversial. We show that 6mA randomly accumulates in early embryos of the cnidarianHydractinia symbiolongicarpus, with a peak at the 16‐cell stage followed by clearance to background levels two cell cycles later, at the 64‐cell stage—the embryonic stage at which zygotic genome activation occurs in this animal. Knocking downAlkbh1, a putative initiator of animal 6mA clearance, resulted in higher levels of 6mA at the 64‐cell stage and a delay in the initiation of zygotic transcription. Our data are consistent with 6mA originating from recycled nucleotides of degraded m6A‐marked maternal RNA postfertilization. Therefore, while 6mA does not function as an epigenetic mark inHydractinia, its random incorporation into the early embryonic genome inhibits transcription. In turn, Alkbh1 functions as a genomic 6mA “cleaner,” facilitating timely zygotic genome activation. Given the random nature of genomic 6mA accumulation and its ability to interfere with gene expression, defects in 6mA clearance may represent a hitherto unknown cause of various pathologies.
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- Award ID(s):
- 1923259
- PAR ID:
- 10429017
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- The EMBO Journal
- Volume:
- 42
- Issue:
- 15
- ISSN:
- 0261-4189
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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