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Open Access Research

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

Shin-ichiro Takebayashi1, Ienglam Lei234, Tyrone Ryba1, Takayo Sasaki1, Vishnu Dileep1, Dana Battaglia1, Xiaolin Gao23, Peng Fang23, Yong Fan23, Miguel A Esteban5, Jiong Tang6, Gerald R Crabtree6, Zhong Wang234 and David M Gilbert1*

Author Affiliations

1 Department of Biological Science, Florida State University, 319 Stadium Drive, Tallahassee, FL, 32306, USA

2 Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Richard Simches Research Center, 185 Cambridge Street, Boston, MA, 02114, USA

3 Harvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA, 02138, USA

4 Department of Cardiac Surgery, Cardiovascular Research Center, University of Michigan Medical School, North Campus Research Complex, Ann Arbor, MI, 48109, USA

5 Stem Cell and Cancer Biology Group, Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China

6 Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA

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Epigenetics & Chromatin 2013, 6:42  doi:10.1186/1756-8935-6-42

Published: 13 December 2013

Abstract

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.

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.

Keywords:
Replication domains; Replication timing; esBAF complex; Chromosome; Developmental regulation