Dynamic phosphorylation of FOXA1 by Aurora B guides post-mitotic gene reactivation
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ABSTRACT:
PROVIDER: PRJNA1142976 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30097921_1.fastq.gz | Fastqsanger.gz | |||
| SRR30097921_2.fastq.gz | Fastqsanger.gz | |||
| SRR30097922_1.fastq.gz | Fastqsanger.gz | |||
| SRR30097922_2.fastq.gz | Fastqsanger.gz | |||
| SRR30097923_1.fastq.gz | Fastqsanger.gz |
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Project description:FOXA1 serves as a crucial pioneer transcription factor in developmental processes, and plays a pivotal role as a mitotic bookmarking factor to perpetuate gene expression profiles and maintain cellular identity. During mitosis, the majority of FOXA1 dissociates from specific DNA binding sites and redistributes to non-specific binding sites, however, the regulatory mechanisms governing FOXA1's molecular dynamics in mitosis remain elusive. Here we show that mitotic kinase Aurora B regulates FOXA1's different DNA binding modes and the formation of the biomolecular condensate. Mechanistically, Aurora B kinase phosphorylates FOXA1 at Serine 221 (S221) to disrupt the specific, but not the non-specific, DNA binding. The phosphorylation of S221 also negatively regulates the FOXA1 condensates that require specific DNA binding. Importantly, perturbation of the dynamic phosphorylation impairs accurate gene reactivations and cell proliferation, suggesting that reversible mitotic protein phosphorylation emerges as a fundamental mechanism for the spatiotemporal control of mitotic bookmarking.
2024-08-31 | GSE273759 | GEO
Project description:During mitosis, RNA polymerase and most transcription factors are excluded from the chromosomes and transcription ceases. The transcriptional re-activation of the genome, following mitosis, requires the re-setting of cell-type specific programs that were initially established during development. However, only about one-fifth of transcription factors are retained on chromosomes throughout mitosis and a subset of these have been shown to facilitate target gene reactivation during mitotic exit. How such M-bM-^@M-^\bookmarkingM-bM-^@M-^] factors bind to chromatin in mitosis and re-activate transcription is central to the stability of transcriptional programs across multiple cell cycles. We compared a diverse set of transcription factors involved in liver differentiation and found different modes of mitotic chromosome binding. The pioneer transcription factor FoxA1, which is among the first to bind liver genes in development, exhibits virtually complete mitotic chromosome binding, whereas other liver factors bind with a range of efficiencies. Yet genome-wide analysis shows that only about 15% of the FoxA1 interphase target sites are bound in mitosis; the latter include sites at genes for maintaining cell differentiation. FoxA1 mutants that perturb specific and nonspecific DNA binding reveal a significant contribution of nonspecific binding events in mitotic chromatin. Such nonspecific binding appears to spread from interphase FoxA1 targets and may serve as storage sites. The hierarchy of specific binding, nonspecific binding, partial chromatin binding, and failure to bind mitotic chromosomes reflects the temporal sequence of the factorsM-bM-^@M-^Y developmental roles in gene activation. Three replicate chIP-seq data sets each are included for mitotic and asynchronously cycling cells; a single input lane from each condition is also included.
2013-03-31 | E-GEOD-39241 | biostudies-arrayexpress
Project description:During mitosis, RNA polymerase and most transcription factors are excluded from the chromosomes and transcription ceases. The transcriptional re-activation of the genome, following mitosis, requires the re-setting of cell-type specific programs that were initially established during development. However, only about one-fifth of transcription factors are retained on chromosomes throughout mitosis and a subset of these have been shown to facilitate target gene reactivation during mitotic exit. How such “bookmarking” factors bind to chromatin in mitosis and re-activate transcription is central to the stability of transcriptional programs across multiple cell cycles. We compared a diverse set of transcription factors involved in liver differentiation and found different modes of mitotic chromosome binding. The pioneer transcription factor FoxA1, which is among the first to bind liver genes in development, exhibits virtually complete mitotic chromosome binding, whereas other liver factors bind with a range of efficiencies. Yet genome-wide analysis shows that only about 15% of the FoxA1 interphase target sites are bound in mitosis; the latter include sites at genes for maintaining cell differentiation. FoxA1 mutants that perturb specific and nonspecific DNA binding reveal a significant contribution of nonspecific binding events in mitotic chromatin. Such nonspecific binding appears to spread from interphase FoxA1 targets and may serve as storage sites. The hierarchy of specific binding, nonspecific binding, partial chromatin binding, and failure to bind mitotic chromosomes reflects the temporal sequence of the factors’ developmental roles in gene activation.
2013-03-31 | GSE39241 | GEO
Project description:Mitotic bookmarking transcription factors (TFs) are thought to mediate rapid and accurate post-mitotic gene reactivation. However, the loss of individual bookmarking TFs often leads to the deregulation of only a small proportion of their mitotic targets, raising doubts on the significance and importance of their bookmarking function. Here, we used targeted proteomics of the mitotic bookmarking TF ESRRB, an orphan nuclear receptor, to discover an unexpected redundancy among members of the protein superfamily of nuclear receptors. Focusing on the nuclear receptor NR5A2, which together with ESRRB is essential in maintaining pluripotency in mouse embryonic stem cells, we demonstrate conjoint bookmarking activity of both factors on promoters and enhancers of a large fraction of active genes, particularly the most rapidly and strongly reactivated ones. Upon fast and simultaneous degradation of both factors during mitotic exit, hundreds of mitotic targets of ESRRB/NR5A2, including key players of the pluripotency network, display attenuated transcriptional reactivation. We propose that redundancy in mitotic bookmarking TFs, especially nuclear receptors, confers robustness to the reestablishment of gene regulatory networks after mitosis.
2023-11-20 | PXD038950 | Pride
Project description:The genome is thought to be transcriptionally silent during mitosis. Technical limitations have prevented the sensitive mapping of mitotic transcription and transcription reactivation during mitotic exit, and thus the networks by which transcriptome dynamics govern the generation of daughter cells have been unclear. We used 5-ethynyluridine to pulse-label intact transcripts during mitosis and mitotic exit and find that the first round of transcription activates genes that are involved in macromolecular synthesis, rather than cell identity. Many interphase genes exhibit residual transcription in mitosis, as confirmed by different methods of assessment, and a subset of genes are more highly transcribed in mitosis than in interphase. We suggest that mitotic transcription may serve an epigenetic function in restoring proper transcription patterns during mitotic exit.
2017-09-20 | GSE87476 | GEO
Project description:Mitotic bookmarking transcription factors (TFs) are thought to mediate rapid and accurate post-mitotic gene reactivation. However, the loss of individual bookmarking TFs often leads to the deregulation of only a small proportion of their mitotic targets, raising doubts on the significance and importance of their bookmarking function. Here, we used targeted proteomics of the mitotic bookmarking TF ESRRB, an orphan nuclear receptor, to discover an unexpected redundancy among members of the protein superfamily of nuclear receptors. Focusing on the nuclear receptor NR5A2, which together with ESRRB is essential in maintaining pluripotency in mouse embryonic stem cells, we demonstrate conjoint bookmarking activity of both factors on promoters and enhancers of a large fraction of active genes, particularly the most rapidly and strongly reactivated ones. Upon fast and simultaneous degradation of both factors during mitotic exit, hundreds of mitotic targets of ESRRB/NR5A2, including key players of the pluripotency network, display attenuated transcriptional reactivation. We propose that redundancy in mitotic bookmarking TFs, especially nuclear receptors, confers robustness to the reestablishment of gene regulatory networks after mitosis.
2022-12-06 | GSE220253 | GEO
Project description:Mitotic bookmarking by CTCF and fast post-mitotic gene reactivation in ES cells
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