Mitotic genome-bookmarking by nuclear hormone receptors: A novel dimension in epigenetic reprogramming and disease assessment

Rizvi, Sheeba; Chhabra, Ayushi; Tripathi, Anjali; Tyagi, Rakesh K.

doi:10.1016/j.mce.2023.112069

Cited by 6 publications

(4 citation statements)

References 67 publications

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“…Interest in the mitotic bookmarking theory increased with the use of live-cell imaging of TFs fused with fluorescent proteins (FPs) or fluorescently labeled tags. This approach led to the identification of several TFs as highly enriched on mitotic chromosomes, including FOXA1, GATA1, Oct4, and Sox2 [ 12 , 14 , 15 ], and other factors such as androgen receptor (AR) and Pregnane and Xenobiotic Receptor (PXR) [ 11 , 16 , 17 ]. In many cases, however, enrichment on mitotic chromosomes as measured by live-cell imaging did not correspond well with site-specific binding as measured through ChIP-based assays.…”

Section: Mitotic Bookmarking: a Historical Perspectivementioning

confidence: 99%

“…However, several studies uncovered that formaldehyde fixation of mitotic cells leads to the exclusion of TFs from mitotic chromosomes [ 12 , 13 ]. Subsequent studies further showed that when examined under live-cell imaging, most TFs show varying degrees of enrichment on mitotic chromosomes ( Figure 1C ) [ 11 , 12 , 14–17 ]. Furthermore, through methodologies that examine TF dynamics, these TF-mitotic interactions are found to be more dynamic than previously observed [ 8 , 10 , 12 , 18 ], suggesting that TF dynamics may play an important role in reactivating transcription programs following mitosis.…”

Section: Introductionmentioning

confidence: 99%

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A dynamic role for transcription factors in restoring transcription through mitosis

Budzyński,

Wong,

Faghihi

et al. 2024

Biochemical Society Transactions

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Mitosis involves intricate steps, such as DNA condensation, nuclear membrane disassembly, and phosphorylation cascades that temporarily halt gene transcription. Despite this disruption, daughter cells remarkably retain the parent cell's gene expression pattern, allowing for efficient transcriptional memory after division. Early studies in mammalian cells suggested that transcription factors (TFs) mark genes for swift reactivation, a phenomenon termed ‘mitotic bookmarking’, but conflicting data emerged regarding TF presence on mitotic chromosomes. Recent advancements in live-cell imaging and fixation-free genomics challenge the conventional belief in universal formaldehyde fixation, revealing dynamic TF interactions during mitosis. Here, we review recent studies that provide examples of at least four modes of TF–DNA interaction during mitosis and the molecular mechanisms that govern these interactions. Additionally, we explore the impact of these interactions on transcription initiation post-mitosis. Taken together, these recent studies call for a paradigm shift toward a dynamic model of TF behavior during mitosis, underscoring the need for incorporating dynamics in mechanistic models for re-establishing transcription post-mitosis.

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Section: Mitotic Bookmarking: a Historical Perspectivementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A dynamic role for transcription factors in restoring transcription through mitosis

Budzyński,

Wong,

Faghihi

et al. 2024

Biochemical Society Transactions

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“…In pluripotent cells socalled bookmarking functions have been revealed where mitotic complexes sustain nucleosome free positioning at genomic sites required for post-mitotic immediate transcriptional reactivation (16)(17)(18)(19). There is some evidence to suggest that nuclear-resident Type II NRs can undertake bookmarking on mitotic chromatin (16,(20)(21)(22). To date, NR-mediated bookmark mechanisms have neither been investigated in PCa nor cancer generally and could add further to understanding of crosstalk mechanisms between NRs.…”

Section: Introductionmentioning

confidence: 99%

“…There is some evidence to suggest that nuclear-resident Type II NRs can also impact gene regulation mechanisms by bookmarking genomic sites on mitotic chromatin (35,39,(41)(42)(43)(44). The orphan receptors NR3B2/ERR2 and NR5A2/LRH-1 (45) can bookmark genomic binding sites during mitosis for other transcription factors to bind subsequently (42,(46)(47)(48). NR-mediated bookmark mechanisms have not been investigated in either PCa or cancer generally and could add further to understanding of crosstalk mechanisms between NRs.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic disruption of the RARγ complex impairs its function to bookmark AR enhancer interactions required for enzalutamide sensitivity in prostate cancer

Wani,

Hussain,

Gray

et al. 2023

Preprint

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Lineage plasticity in advanced prostate cancer (PCa) involves a corruption of differentiation programs, often regulated by the androgen receptor (AR). This study explores an under-explored cistromic mechanism: how type II nuclear receptors like RARγ may affect AR control of prodifferentiation transcriptional programs. The components of the RARγ complex are dynamic in PCa cell models and enriched for miR-96 targets, partly due to m6A-marked miR-96 recognition elements. Restoration of TACC1 and RARγ, both miR-96 repressed targets, in 22Rv1 cells augmented the AR cistrome, particularly in active enhancers and super-enhancers. In 22Rv1 cells the RARγ complex was enriched for bookmarking components, and created nucleosome-free chromatin enriched for H3K27ac, and profoundly enhanced the dihydrotestosterone (DHT)-dependent AR cistrome in G2/M cells and are all indicative of bookmarking functions. The RARγ-dependent and DHT-regulated AR cistrome-transcriptome relationships were significantly strengthened, notably in Active Enhancers, associated with AR-dependent luminal differentiation transcriptional programs. Interestingly RARγ-dependent AR cistromes significantly overlapped with ONECUT2, but the comparative transcriptional analyses supported an antagonistic function between RARγ and ONECUT2. Finally, the footprint of these data was detected in advanced tumors. For example, the miR-96 targetome and RARγ/ONECUT2 antagonized genes were significantly similar to AR signaling inhibitor-induced alternative lineages and metastatic tumors. Partial correlation analyses revealed RARγ CoAs identified by RIME, including SSRP1, significantly strengthened the correlations between AR and RARγ-TACC1-dependent DHT-regulated target genes in SU2C advanced PCa, and differentially-expressed genes between tumors with high RARγ and low ONECUT2 expression compared to the reverse was significantly associated with elevated AR score. In summary, the RARγ complex, selectively targeted by miR-96 functions as an enhancer re-programmer by bookmarking chromatin in G2/M cells to sustain and restrict AR transcriptional competency required for programs such as luminal differentiation, and antagonizing ONECUT2.

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Nuclear localization signal in nuclear receptor VDR facilitates the mitotic genome bookmarking by involving distinct amino acid residues

Kashyap,

Chhabra,

Kumari

et al. 2024

Molecular and Cellular Endocrinology

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Mitotic genome-bookmarking by nuclear hormone receptors: A novel dimension in epigenetic reprogramming and disease assessment

Cited by 6 publications

References 67 publications

A dynamic role for transcription factors in restoring transcription through mitosis

A dynamic role for transcription factors in restoring transcription through mitosis

Epigenetic disruption of the RARγ complex impairs its function to bookmark AR enhancer interactions required for enzalutamide sensitivity in prostate cancer

Nuclear localization signal in nuclear receptor VDR facilitates the mitotic genome bookmarking by involving distinct amino acid residues

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