Murine esBAF chromatin remodeling complex subunits BAF250a and Brg1 are necessary to maintain and reprogram pluripotency-specific replication timing of select replication domains

小鼠 esBAF 染色质重塑复合物亚基 BAF250a 和 Brg1 是维持和重新编程选择性复制域的多能性特异性复制时间所必需的

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作者:Shin-Ichiro Takebayashi, Ienglam Lei, Tyrone Ryba, Takayo Sasaki, Vishnu Dileep, Dana Battaglia, Xiaolin Gao, Peng Fang, Yong Fan, Miguel A Esteban, Jiong Tang, Gerald R Crabtree, Zhong Wang, David M Gilbert

Background

Cellular differentiation and reprogramming are accompanied by changes in replication timing and 3D organization of large-scale (400 to 800 Kb) chromosomal domains ('replication domains'), but few gene products have been identified whose disruption affects these properties.

Conclusions

Loss of specific esBAF complex subunits alters replication timing of select replication domains in pluripotent cells.

Results

Here we show that deletion of esBAF chromatin-remodeling complex components BAF250a and Brg1, but not BAF53a, disrupts replication timing at specific replication domains. Also, BAF250a-deficient fibroblasts reprogrammed to a pluripotency-like state failed to reprogram replication timing in many of these same domains. About half of the replication domains affected by Brg1 loss were also affected by BAF250a loss, but a much larger set of domains was affected by BAF250a loss. esBAF binding in the affected replication domains was dependent upon BAF250a but, most affected domains did not contain genes whose transcription was affected by loss of esBAF. Conclusions: Loss of specific esBAF complex subunits alters replication timing of select replication domains in pluripotent cells.

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