Title
Developmental control of replication timing defines a new breed of chromosomal domains with a novel mechanism of chromatin unfolding

Shin-ichiro Takebayashi （竹林慎一郎／ 発生医学研究所 細胞医学分野 ）

Abstract:
Several 400-800 kb murine chromosome domains switch from early to late replicating during loss of pluripotency, accompanied by a stable form of gene silencing that is resistant to reprogramming. Here, I show results demonstrating that these domains are amongst the least sensitive regions in the genome to global digestion by either MNase or restriction enzymes. This inaccessible chromatin state persists whether these regions are in their physically distended early replicating or compact late replicating configuration, despite dramatic changes in 3D chromatin folding and long-range chromatin interactions, and despite large changes in transcriptional activity. This contrasts with the strong correlation between early replication, accessibility, transcriptional activity, and open chromatin configuration that is observed genome-wide. The results reveal a novel principle of developmentally regulated large scale chromosome folding involving a sub-nuclear compartment switch of inaccessible chromatin. This unusual level of regulation may underlie resistance to reprogramming in replication timing switch regions. I also discuss factors regulating this level of chromosome organization.

References:
Takebayashi S, Dileep V, Ryba T, Dennis JH, Gilbert DM. Chromatin-interaction compartment switch at developmentally regulated chromosomal domains reveals an unusual principle of chromatin folding. Proc Natl Acad Sci U S A 2012; 109:12574-9.