Establishing Chromatin Regulatory Landscape during Mouse Preimplantation Development

Area of Science:

• Developmental Biology
• Epigenetics
• Genomics

Background:

• The establishment of chromatin regulatory landscapes in the inner cell mass during early embryonic development is poorly understood.
• Differential packaging of sperm and egg genomes presents a challenge for establishing a unified chromatin structure.

Purpose of the Study:

• To investigate the dynamic chromatin regulatory landscape during mouse preimplantation development.
• To identify key transcription factors involved in establishing chromatin accessibility.
• To develop a method for mapping DNase I-hypersensitive sites (DHS) in low-input embryonic samples.

Main Methods:

• Development of a low-input DNase I sequencing (liDNase-seq) technique.
• Generation of DHS maps from mouse preimplantation embryos (1-cell to morula stage).
• Analysis of chromatin accessibility changes and the role of specific transcription factors.

Main Results:

• The DHS landscape is progressively established, with a significant increase observed at the 8-cell stage.
• Paternal chromatin accessibility is rapidly reprogrammed post-fertilization to match maternal chromatin levels.
• Imprinted genes display allelic accessibility bias, and transcription factors Nfya and Oct4 are identified as critical for DHS formation at specific developmental stages.

Conclusions:

• The study reveals the dynamic nature of the chromatin regulatory landscape during early mammalian embryogenesis.
• Nfya is important for zygotic genome activation and early DHS formation (2-cell stage).
• Oct4 plays a role in establishing DHSs at the 8-cell stage, highlighting stage-specific roles of transcription factors in shaping the epigenome.