Abstract
It is well known that both recipient cells and donor nuclei demonstrate a mitotic advantage as observed in the traditional reprogramming with somatic cell nuclear transfer (SCNT). However, it is not known whether a specific mitotic factor plays a critical role in reprogramming. Here we identify an isoform of human bromodomain-containing 3 (BRD3), BRD3R (BRD3 with Reprogramming activity), as a reprogramming factor. BRD3R positively regulates mitosis during reprogramming, upregulates a large set of mitotic genes at early stages of reprogramming, and associates with mitotic chromatin. Interestingly, a set of the mitotic genes upregulated by BRD3R constitutes a pluripotent molecular signature. The two BRD3 isoforms display differential binding to acetylated histones. Our results suggest a molecular interpretation for the mitotic advantage in reprogramming and show that mitosis may be a driving force of reprogramming.
Highlights
It is well known that both recipient cells and donor nuclei demonstrate a mitotic advantage as observed in the traditional reprogramming with somatic cell nuclear transfer (SCNT)
We present evidence that the mitotic protein BRD3R facilitates resetting of the pluripotent cell cycle structure and increases the number of reprogramming-privileged mitotic cells by upregulating as many as 128 mitotic genes, without compromising the p53–p21 surveillance pathway
Since there is a deletion of 178 aa at the C terminus in BRD3R compared with bromodomain-containing 3 (BRD3) and the nuclear localization signal is not defined, we examined its ability of localization into nucleus
Summary
It is well known that both recipient cells and donor nuclei demonstrate a mitotic advantage as observed in the traditional reprogramming with somatic cell nuclear transfer (SCNT). It is not known whether a specific mitotic factor plays a critical role in reprogramming. It is possible that the observed mitotic advantage is a technical artifact associated with SCNT because reprogramming factors within nuclei may have been removed from the interphase recipient cells and are released and remain in the reprogramming-competent mitotic cytoplasts due to the breakdown of nuclear envelopes in mitosis[18,19]. Our findings provide molecular insights into the mitotic advantage of reprogramming
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