Chromatin landscape instructs precise transcription factor regulome during embryonic lineage specification

Area of Science:

• Developmental Biology
• Epigenetics
• Genomics

Background:

• Embryonic development involves complex transcriptional, translational, and metabolic changes.
• Chromatin regulators, including transcription factors (TFs), are critical for regulating these dynamic processes.
• TFAP2C, a trophoblast regulator, is vital for early cell fate decisions but persists post-lineage establishment.

Purpose of the Study:

• To investigate the dynamics of TFAP2C during mouse peri-implantation.
• To elucidate the collaboration between TFAP2C and lineage regulators CDX2 and NANOG.
• To understand the epigenetic mechanisms regulating TFAP2C function and embryonic cell fates.

Main Methods:

• Analysis of TFAP2C dynamics in mouse embryos during the peri-implantation stage.
• Investigation of TFAP2C interactions with CDX2 and NANOG.
• Examination of H3K9me3 formation and its effect on TFAP2C binding to developmental genes.

Main Results:

• TFAP2C exhibits dynamic expression patterns during peri-implantation.
• TFAP2C collaborates with CDX2 and NANOG in regulating lineage identity.
• De novo H3K9me3 formation in extraembryonic ectoderm antagonizes TFAP2C binding, maintaining lineage identity.

Conclusions:

• TFAP2C plays a crucial role in maintaining cell lineage identity post-establishment.
• Epigenetic modifications, specifically H3K9me3, dynamically regulate TFAP2C genomic binding.
• Chromatin plasticity is essential for directing TF binding and regulating embryonic cell fates.