Exploring the cell line-specific spatial chromatin organization during mouse early development
冨川 順子1, 岡村 浩司2, 林 恵子1, 阿久津 英憲3, 田中 智4, 秦 健一郎1, 中林 一彦1|
1成育医療セ・周産期病態, 2成育医療セ・システム医学, 3成育医療セ・生殖医療, 4東大・院農・応用動物
Mammalian genomes are characterized by higher order chromatin organizations that orchestrate spatial and temporal gene regulation.
In mammalian embryogenesis, the Tead4 gene is shown to be critical for the first cell lineage specification: segregation of trophectoderm (TE), which gives rise to the trophoblast of the placenta, from the inner cell mass (ICM).
While differential subcellular localization of the TEAD4 protein between TE and ICM has been shown to be crucial for cell lineage commitment, little is known about the higher order chromatin architectures involved in the transcriptional regulation of Tead4 during early development.
In the present study, as a means to elucidate the mechanisms underlying the spatial and temporal gene expression of Tead4, we applied the circular chromosome conformation capture (4C)-Seq system to the promoter of the Tead4 gene.
We successfully detected 135 and 98 interactions on the Tead4 promoter in mouse embryonic stem (ES) and trophoblast stem (TS) cells, respectively.
These interactions include both inter- and intra-chromosomal interactions.
Consistent with the critical role of Tead4 in the TE lineage, we observed the frequent overlaps of the genomic regions interacting with the Tead4 promoter and open chromatin regions identified by our FAIRE-seq approach only in TS cells, but not in ES cells.
In addition, we identified two putative Tead4 enhancers located -21 kb and -3 kb downstream of the transcription start site of Tead4 in TS cells.
This interactome on the Tead4 promoter could be an important part of the regulatory network operating TE lineage commitment.|