A hyperactive transcriptional state marks genome reactivation at the mitosis-G1 transition

Hsiung, Chris C.-S.; Bartman, Caroline; Huang, Peng; Ginart, Paul; Stonestrom, Aaron J.; Keller, Cheryl A.; Face, Carolyne; Jahn, Kristen S.; Evans, Perry; Sankaranarayanan, Laavanya; Giardine, Belinda; Hardison, R; Raj, Arjun; Blobel, Gerd A.

doi:10.1101/053678

Cited by 7 publications

(10 citation statements)

References 76 publications

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“…Further, the expression of select cell cycle related genes (e.g., CDT1, CDK4, CDK6, and PCNA) was not prominent in 90m G1 samples, but was more apparent in 180m G1 and asynchronous G1 samples ( Figure S2E). These results are consistent with previous reports that indicate that transcription progressively increases in post-mitotic G1 (Hsiung et al, 2016;Palozola et al, 2017). Taken together, these results show that the 90m G1 fraction contained cells in early G1 with condensed chromatin and low transcription, while the 180m G1 fraction contained cells from a later stage of G1 with increased transcriptional activity.…”

Section: Isolation Of Cells From Early or Later G1 Phase Based On Nocsupporting

confidence: 93%

High quality mapping of chromatin at or near the nuclear lamina for small numbers of cells

Tran

Adam

Goldman

et al. 2021

Preprint

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A large fraction of heterochromatin in the metazoan genome is associated with the nuclear lamina (NL) in interphase nuclei. This heterochromatin is often referred to as Lamina-Associated Domains (LADs) and are often mapped from cell populations asynchronously progressing through the cell cycle. We and others have recently reported that LADs are largely stable during G1, S, or G2 phases of the cell cycle, and appear similar to LADs mapped from bulk cell populations. LADs in senescent cells, however, are reported to be quite different from proliferating cells, and it remains unclear how senescent cell LADs are established. As cells finish mitosis and re-enter G1, reassembly of the nuclear envelope and NL appears to precede mitotic chromosome decondensation. Therefore, the initial NL interactions with the decondensing chromatin may be quite different from those reported in asynchronous or FACS isolated G1, S, or G2 populations. By developing a modified version of the Tyramide-Signal Amplification sequencing (TSA-seq), which we call chromatin pull down-based Tyramide Signal Amplification-sequencing (cTSA-seq), we uncover a dynamic NL-chromatin interaction as cells progress through G1. The appearance of stable LADs coincides with sufficient chromatin decondensation and active gene expression in G1. Interestingly, early G1 NL-chromatin interactions, which are found toward the telomeric ends of human chromosomes, are similar to those found in oncogene-induced senescent cells. We find that the assembly of LADs during the formation of the G1 nucleus is gradual and that the arrest of NL-chromatin interactions in early G1 may contribute to genome disorganization of senescence cells.

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Section: Isolation Of Cells From Early or Later G1 Phase Based On Nocsupporting

confidence: 93%

High quality mapping of chromatin at or near the nuclear lamina for small numbers of cells

Tran

Adam

Goldman

et al. 2021

Preprint

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“…Cellular DNA content was monitored with FACS, demonstrating progression through cytokinesis at 1.5-2hr post-release and entry into S-phase beginning at 12hr (Figure 3A). Gene reactivation begins between 1 and 1.5hr following mitosis which is consistent with results from Pol II ChIP-seq (Hsiung, Bartman, et al, 2016) and pulse labeling of RNA (Palozola, Donahue, et al, 2017) (Figure 3B). Additionally, high-resolution nascent RNA profiling methods such as PRO-seq allow the initial waves of polymerase to be detected as it progresses into gene bodies (Figure 3C, D).…”

Section: Genome Reactivation Following Mitosis Is Highly Dynamicsupporting

confidence: 87%

“…In addition to timing of activation, robust transcription of genes is hypothesized to be a contributor to cell-specific gene expression. A recent study in mouse erythroblasts suggested that gene reactivation following mitosis often occurs in a robust burst of transcription (Hsiung, Bartman, et al, 2016). Using our data, we identified 365 "burst" genes whose spike-in normalized expression levels during the time course are greater than expression levels in asynchronous cells (Figure S4E, Methods).…”

Section: Gene Reactivation Classes Are Associated With Distinct Cellular Functionsmentioning

confidence: 92%

“…Waves of gene reactivation were demonstrated, beginning with genes involved in housekeeping functions and rebuilding the cell, while cell type-specific genes reactivated later (Kang, Shokhirev, et al, 2020;Palozola, Donahue, et al, 2017). Profiling of RNAPII with ChIP-seq in mice demonstrated a burst of transcription immediately following mitosis (Hsiung, Bartman, et al, 2016). Interestingly, functional tests of proposed mitotic bookmarks during global transcription reactivation have demonstrated that TBP and histone acetylation are only partially responsible for the reestablishment of transcription (Pelham-Webb, Polyzos, et al, 2021;Teves, An, et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Multiple modes of regulation control dynamic transcription patterns during the mitosis-G1 transition

Villafano

et al. 2021

Preprint

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Following cell division, genomes must reactivate gene expression patterns that reflect the identity of the cell. Here, we use PRO-seq to examine the mechanisms that reestablish transcription patterns after mitosis. We uncover regulation of the transcription cycle at multiple steps including initiation, promoter-proximal pause positioning and escape, poly-A site cleavage and termination during the mitotic-G1 transition. During mitosis, RNA polymerase activity is retained at initiation sites, albeit shifted in position relative to non-mitotic cells. This activity is strongly linked to maintenance of local chromatin architecture during mitosis and is more predictive of rapid gene reactivation than histone modifications previously associated with bookmarking. These molecular bookmarks, combined with sequence-specific transcription factors, direct expression of select cell growth and cell specific genes during mitosis followed by reactivation of functional gene groups with distinct kinetics after mitosis. This study details how dynamic regulation of transcription at multiple steps contributes to gene expression during the cell cycle.

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“…maintain sequence-specific binding throughout mitosis) may be higher in this hierarchy. Emerging genome-wide studies mapping histone marks during M-G1 transition, should help dissecting further the role of TFs during this period (Hsiung et al 2016;Javasky et al 2018;Kang et al 2020).…”

Section: Resultsmentioning

confidence: 99%

Hierarchical reactivation of transcription during mitosis-to-G1 transition by Brn2 and Ascl1 in neural stem cells

Soares

Teixeira

et al. 2021

Preprint

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During mitosis, chromatin condensation is accompanied by a global arrest of transcription. Recent studies suggest transcriptional reactivation upon mitotic exit occurs in temporally coordinated waves, but the underlying regulatory principles have yet to be elucidated. In particular, the contribution of sequence-specific transcription factors (TFs) remains poorly understood. Here we report that Brn2, an important regulator of neural stem cell identity, associates with condensed chromatin throughout cell division, as assessed by live-cell imaging of proliferating neural stem cells. By contrast, the neuronal fate determinant Ascl1 dissociates from mitotic chromosomes. ChIP-seq analysis reveals that Brn2 mitotic-chromosome binding does not result in sequence-specific interactions prior to mitotic exit, relying mostly on electrostatic forces. Nevertheless, surveying active transcription using single-molecule RNA-FISH against immature transcripts, indicates the differential presence of TF near chromatin when exiting mitosis is associated with early (anaphase) versus late (early G1) reactivation of key targets of Brn2 and Ascl1, respectively. Moreover, by using a mitotic-specific dominant negative approach, we show that competing with Brn2 binding during mitotic exit reduces the transcription of its target gene Nestin. Our study shows an important role for differential binding of TFs to mitotic chromosomes, governed by their electrostatic properties, in defining the temporal order of transcriptional reactivation during mitosis-to-G1 transition.

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A hyperactive transcriptional state marks genome reactivation at the mitosis-G1 transition

Cited by 7 publications

References 76 publications

High quality mapping of chromatin at or near the nuclear lamina for small numbers of cells

High quality mapping of chromatin at or near the nuclear lamina for small numbers of cells

Multiple modes of regulation control dynamic transcription patterns during the mitosis-G1 transition

Hierarchical reactivation of transcription during mitosis-to-G1 transition by Brn2 and Ascl1 in neural stem cells

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