A Hyperactive Transcriptional State Marks Genome Reactivation During Mitotic Exit

BLOOD(2015)

引用 23|浏览31
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摘要
The tremendous proliferative capacity of erythroid precursor cells underlies the production of over a million red blood cells per second in adult humans. During every mitosis the mammalian nucleus is disassembled and transcriptionally silent. Genome reactivation after mitosis is a key step in the propagation of transcriptional programs through cell generations, yet how this occurs remains largely unexplored. We carried out the first genome wide survey of transcription in cells emerging from mitosis using RNA polymerase II ChIP seq in purified populations at various post-mitotic time points. Using unsupervised approaches, we discover and classify genome reactivation patterns among genes. A surprisingly large fraction of genes (~25%) displays a post-mitotic spike in transcription. This spike represents the first complete round of transcription and accounts for the greatest gene-to-gene variance in temporal patterns of transcription in G1 phase. Another notable and contrasting pattern is gene activation late in the G1 phase. Single-molecule RNA FISH imaging demonstrates that the post-mitotic transcriptional spike represents the highest activity throughout the cell cycle and results in an increase in mature mRNAs, indicating that the phenomenon has the capacity to alter gene expression. Surprisingly, the post-mitotic transcriptional spike occurs independent of enhancer action and can be recapitulated with promoter sequences ectopically integrated into the genome. In contrast, late-G1 gene reactivation is distinct and requires enhancer function. Our findings uncover novel modes of transcriptional control during exit from mitosis with implications for our understanding of transitions in gene expression states in dividing cells. Disclosures No relevant conflicts of interest to declare.
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