Researchers characterize mechanism for regulating orderly zygotic genome activation in early embryos

Early development of an embryo is solely supported by maternally deposited RNAs and proteins until its own genome is activated through a process called zygotic genome activation (ZGA).

Recent research by Chinese scientists has revealed novel molecular mechanisms by which HIRA acts in concert with dPCIF1 to establish a totipotent chromatin and facilitate orderly zygotic genome activation in the early embryos of Drosophila.

Results of the study were published in PNAS on Nov. 14 as “HIRA and dPCIF1 coordinately establish totipotent chromatin and control orderly ZGA in Drosophila embryos.”

The zygotic genome remains transcriptionally silent in the early stage, and the early embryo undergoes profound changes in its genomic architecture and reprograms chromatin from a germ cell into a totipotent state. During the maternal-to-zygotic transition in Drosophila, the pioneer transcription factors Zelda and GAF jointly regulate the transcriptional activation of zygotic genes in the early embryo, ensuring proper embryonic development. 

Prof. SUN Qinmiao and her group from the Institute of Zoology of the Chinese Academy of Sciences, collaborated with CHEN Dahua’s group from the Biomedical Research Institute of Yunnan University to unravel the mechanisms of establishment and maintenance of the totipotent chromatin state in early embryos. They also studied how pioneer transcription factors are regulated to initiate gene expression in a timely, orderly manner during early embryonic development.

The researchers investigated the function of dPCIF1 and found that maternal depletion of dPCIF1 leads to significant embryonic lethality. Maternal depletion of dPCIF1 also results in a significant increase in the distribution of the pioneer transcription factor GAF on early embryonic chromatin, indicating that in the early embryo, dPCIF1 maintains normal zygotic genome activation by antagonizing the function of GAF.

Further research revealed that the specific histone H3.3 chaperone HIRA interacts with both dPCIF1 and GAF in the early embryo. Maternal depletion of HIRA causes complete embryonic lethality and a general downregulation of zygotic gene expression, with the downregulated zygotic genes being highly consistent with those prematurely activated in embryos with maternal depletion of dPCIF1.

“dPCIF1 acts as a surveillance factor, assisting HIRA in achieving orderly zygotic genome activation by controlling the premature activation of GAF,” said Prof. SUN.

By identifying a novel mechanism for the orderly regulation of zygotic gene activation during early embryonic development, this research provides new insights into the regulatory mechanisms of zygotic gene activation.

The study was supported by the National Natural Science Foundation of China and the National Key R&D Program of the Ministry of Science and Technology of China.