The acetyllysine reader BRD3R promotes human nuclear reprogramming and regulates mitosis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE66798 | GEO | 2016/03/01
SECONDARY ACCESSION(S): PRJNA277980
REPOSITORIES: GEO
Similar Datasets
Project description: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. Human BJ cells transduced with lentiviral particles of the conventional reprogramming factors (OCT3/4, SOX2 and KLF4) were used as controls. Two types of controls were used: 1) BJ transduced with OSK (OCT4, SOX2 and KFL4) viruses; 2) BJ cells transduced with OSK plus GFP viruses. Experimental treatment was BJ cells transduced with OSK plus BRD3R viruses. RNA was extracted from cells at day 3 of reprogramming because the reprogramming cells are still homogeneous and transgenes are well expressed at this time point.
2016-03-01 | E-GEOD-66798 | biostudies-arrayexpress
Project description:Entry into and exit from mitosis is driven by precisely-timed changes in protein abundance, and involves transcriptional regulation and protein degradation. However, the role of translational regulation in modulating cellular protein content during mitosis remains poorly understood. Here, using ribosome profiling, we show that translational, rather than transcriptional regulation is the dominant mechanism for modulating protein synthesis at mitotic entry. The vast majority of regulated mRNAs are translationally repressed, which contrasts previous findings of selective mRNA translational activation at mitotic entry. One of the most pronounced translationally repressed genes in mitosis is Emi1, an inhibitor of the anaphase promoting complex (APC), which is degraded during mitosis. We show that Emi1 degradation is insufficient for full APC activation and that simultaneous translational repression is required. These results provide a genome-wide view of protein translation during mitosis and suggest that translational repression may be used to ensure complete protein inactivation Ribosome profiling and mRNA-seq from 3 time points in the cell cycle
2015-09-01 | E-GEOD-67902 | biostudies-arrayexpress
Project description:Mitosis entails global alterations to chromosome structure and nuclear architecture, concomitant with transient silencing of transcription. How cells transmit transcriptional states through mitosis remains incompletely understood. While many nuclear factors dissociate from mitotic chromosomes, the observation that certain nuclear factors and chromatin features remain associated with individual loci during mitosis originated the hypothesis that they could provide transcriptional memory through mitosis. To obtain the first genome-wide view of the dynamics of chromatin structure during mitosis, we compared the DNase sensitivity of interphase and mitotic chromatin at two stages of cellular maturation in a rapidly dividingmurine erythroblastmodel. Despite global chromosome condensation visible during mitosis at the microscopic level, the chromatin accessibility landscape is largely unaltered. However, mitotic chromatin accessibility is locally dynamic, with individual loci maintaining none, some, or all of their interphase accessibility. Mitotic reduction in accessibility occurs primarily within narrow, highly hypersensitive sites that frequently coincide with transcription factor binding sites, whereas broader domains of moderate accessibility tend to be more stable. In mitosis, proximal promoters generally maintain their accessibility, whereas distal regulatory elements preferentially lose accessibility. Promoters with the highest degree of accessibility preservation in mitosis tend to also be accessible across many murine tissues in interphase. Transcription factor GATA1 exerts site-specific changes in interphase accessibility that are most pronounced at distal regulatory elements, but does not visibly influence mitotic accessibility. We conclude that features of open chromatin are remarkably stable through mitosis and are modulated at the level of individual genes and regulatory elements. Dnase-Seq data is integrated with Chip-seq [GSE36589, GSE30142] and RNA-seq to examine epigentic changes in mitosis. We performed DNase-seq on two cell lines, G1E and G1E-ER4, both on an asynchronus population, and on a sample of cells in mitosis; each of the 4 experiments in triplicate.
2014-10-01 | E-GEOD-61885 | biostudies-arrayexpress
Project description:Mitotic bookmarking transcription factors (BFs) maintain the capacity to bind to their targets during mitosis, despite major rearrangements of the chromatin. While they were thought to propagate gene regulatory information through mitosis by statically occupying their DNA targets, it has recently become clear that BFs are highly dynamic in mitotic cells. This represents both a technical and a conceptual challenge to study and understand the function of BFs: first, formaldehyde has been suggested to be unable to efficiently capture these transient interactions, leading to profound contradictions in the literature; second, if BFs are not permanently bound to their targets during mitosis, it becomes unclear how they convey regulatory information to daughter cells. Here, comparing formaldehyde to alternative fixatives we clarify the nature of the chromosomal association of previously proposed BFs in embryonic stem cells: while ESRRB can be considered as a canonical BF that binds at selected regulatory regions in mitosis, SOX2 and OCT4 establish DNA sequence independent interactions with the mitotic chromosomes, either throughout the chromosomal arms (SOX2) or at pericentromeric regions (OCT4). Moreover, we show that ordered nucleosomal arrays are retained during mitosis at ESRRB bookmarked sites, whereas regions losing transcription factor binding display a profound loss of order. By maintaining nucleosome positioning during mitosis, ESRRB might ensure the rapid post-mitotic re-establishment of functional regulatory complexes at selected enhancers and promoters. Our results provide a mechanistic framework that reconciles dynamic mitotic binding with the transmission of gene regulatory information across cell division.
2018-12-04 | GSE122589 | GEO
Project description:Entry into and exit from mitosis is driven by precisely-timed changes in protein abundance, and involves transcriptional regulation and protein degradation. However, the role of translational regulation in modulating cellular protein content during mitosis remains poorly understood. Here, using ribosome profiling, we show that translational, rather than transcriptional regulation is the dominant mechanism for modulating protein synthesis at mitotic entry. The vast majority of regulated mRNAs are translationally repressed, which contrasts previous findings of selective mRNA translational activation at mitotic entry. One of the most pronounced translationally repressed genes in mitosis is Emi1, an inhibitor of the anaphase promoting complex (APC), which is degraded during mitosis. We show that Emi1 degradation is insufficient for full APC activation and that simultaneous translational repression is required. These results provide a genome-wide view of protein translation during mitosis and suggest that translational repression may be used to ensure complete protein inactivation
2015-09-01 | GSE67902 | GEO
Project description:Regulated start-codon selection has the potential to reshape the proteome through the differential production of upstream open reading frames, canonical proteins, and alternative translational isoforms. However, conditions under which start codon selection is altered remain poorly defined. Here, using transcriptome-wide translation-initiation-site profiling, we reveal a global increase in the stringency of start-codon selection during mammalian mitosis. Low-efficiency initiation sites are preferentially repressed in mitosis, resulting in pervasive changes in the translation of thousands of start sites and their corresponding protein products. This enhanced stringency of start-codon selection during mitosis results from increased association between the 40S ribosome and the key regulator of start-codon selection, eIF1. We find that increased eIF1–40S ribosome interaction during mitosis is mediated by the release of a nuclear pool of eIF1 upon nuclear envelope breakdown. Selectively depleting the nuclear pool of eIF1 eliminates the change to translational stringency during mitosis, resulting in altered synthesis of thousands of protein isoforms. In addition, preventing mitotic translational rewiring results in substantially increased cell death and decreased mitotic slippage in cells that experience a mitotic delay induced by anti-mitotic chemotherapies. Thus, cells globally control stringency of translation initiation, which has critical roles during the mammalian cell cycle in preserving mitotic cell physiology.
2023-12-02 | GSE230189 | GEO
Project description:Mitosis entails global alterations to chromosome structure and nuclear architecture, concomitant with transient silencing of transcription. How cells transmit transcriptional states through mitosis remains incompletely understood. While many nuclear factors dissociate from mitotic chromosomes, the observation that certain nuclear factors and chromatin features remain associated with individual loci during mitosis originated the hypothesis that they could provide transcriptional memory through mitosis. To obtain the first genome-wide view of the dynamics of chromatin structure during mitosis, we compared the DNase sensitivity of interphase and mitotic chromatin at two stages of cellular maturation in a rapidly dividingmurine erythroblastmodel. Despite global chromosome condensation visible during mitosis at the microscopic level, the chromatin accessibility landscape is largely unaltered. However, mitotic chromatin accessibility is locally dynamic, with individual loci maintaining none, some, or all of their interphase accessibility. Mitotic reduction in accessibility occurs primarily within narrow, highly hypersensitive sites that frequently coincide with transcription factor binding sites, whereas broader domains of moderate accessibility tend to be more stable. In mitosis, proximal promoters generally maintain their accessibility, whereas distal regulatory elements preferentially lose accessibility. Promoters with the highest degree of accessibility preservation in mitosis tend to also be accessible across many murine tissues in interphase. Transcription factor GATA1 exerts site-specific changes in interphase accessibility that are most pronounced at distal regulatory elements, but does not visibly influence mitotic accessibility. We conclude that features of open chromatin are remarkably stable through mitosis and are modulated at the level of individual genes and regulatory elements.
2014-10-01 | GSE61885 | GEO
Project description:Here we compare the distribution of insulator proteins during interphase and mitosis. We performed ChIP-seq analysis on purified populations of interphase and mitotic Kc cells, using antibodies against CP190, dCTCF, BEAF, and Su(Hw). Examination of 4 different insulator proteins during interphase and mitosis
2013-01-21 | E-GEOD-32584 | biostudies-arrayexpress
Project description:Tissue-specific transcription patterns are preserved throughout cell divisions to maintain lineage fidelity. We investigated whether transcription factor GATA1 plays a role in transmitting hematopoietic gene expression programs through mitosis when transcription is transiently silenced. Live cell imaging revealed that a fraction of GATA1 is retained focally within mitotic chromatin. ChIP-seq of highly purified mitotic cells uncovered that key hematopoietic regulatory genes are occupied by GATA1 in mitosis. The GATA1 co- regulators FOG1 and TAL1 dissociate from mitotic chromatin, suggesting that GATA1 functions as platform for their postmitotic recruitment. Mitotic GATA1 target genes tend to re-activate more rapidly upon entry into G1 than genes from which GATA1 dissociates. A novel system designed to destroy GATA1 specifically during mitosis revealed that mitotic occupancy is required for rapid target gene reactivation. These studies suggest a requirement of mitotic “bookmarking” by GATA1 for the faithful propagation of cell type-specific transcription programs through cell division GATA1 occupancy profiles in mitotic G1E-ER4 +E2 cells generated by ChIP-sequencing. ChIP input DNA was sequenced as control. Previously reported (GSE18164) GATA1 occupancy in asynchrnous G1E-ER4 +E2 cells was analysed and compared with mitotic GATA1 occupancy.
2012-08-17 | E-GEOD-36589 | biostudies-arrayexpress
Project description:Tissue-specific transcription patterns are preserved throughout cell divisions to maintain lineage fidelity. We investigated whether transcription factor GATA1 plays a role in transmitting hematopoietic gene expression programs through mitosis when transcription is transiently silenced. Live cell imaging revealed that a fraction of GATA1 is retained focally within mitotic chromatin. ChIP-seq of highly purified mitotic cells uncovered that key hematopoietic regulatory genes are occupied by GATA1 in mitosis. The GATA1 co- regulators FOG1 and TAL1 dissociate from mitotic chromatin, suggesting that GATA1 functions as platform for their postmitotic recruitment. Mitotic GATA1 target genes tend to re-activate more rapidly upon entry into G1 than genes from which GATA1 dissociates. A novel system designed to destroy GATA1 specifically during mitosis revealed that mitotic occupancy is required for rapid target gene reactivation. These studies suggest a requirement of mitotic “bookmarking” by GATA1 for the faithful propagation of cell type-specific transcription programs through cell division
2012-08-17 | GSE36589 | GEO