Abstract
BackgroundCellular 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.ResultsHere 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.ConclusionsLoss of specific esBAF complex subunits alters replication timing of select replication domains in pluripotent cells.
Highlights
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
We found that the embryonic stem cellspecific Brahma-associated factor (BAF) complex complex deficiency leads to alterations of replication timing both in ESCs and during cellular reprogramming
Loss of Brahma-related gene 1 (Brg1), but not BAF53a, affects an overlapping set of replication domains Since BAF250a is a subunit of the embryonic stem cellspecific BAF complex (esBAF) complex in ESCs [32], we examined the role of two other esBAF subunits, Brg1 and BAF53a, in the regulation of replication domain structures
Summary
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. Developmental changes in chromosome structure can occur at the level of large, often megabase-sized chromosome domains [1,2,3,4,5] This cell type-specific chromosomal domain structure is thought to be important for coordinating expression of genes, thereby ensuring proper development of embryos. Replication timing of rDNA was shown to be affected by mutations in the rDNA-specific chromatin remodeling complex NoRC [20] Together, these results suggest that specific gene products should eventually be identified that regulate cell type and domain-specific affects. Inspired by the specific and dramatic effect of NoRC on regulation of rDNA replication timing, we investigated the role of cell type specific chromatin remodeling complexes in replication timing changes during embryonic stem cell differentiation
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
