Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide binding profiles of HP1a and Prospero in Drosophila central brain neural precursors and neurons

ABSTRACT: Compacted heterochromatin blocks are prevalent in differentiated cells and present a barrier to cellular reprogramming. It remains obscure how heterochromatin remodeling is orchestrated during cell differentiation. Here we find that the evolutionarily conserved homeodomain transcription factor Prospero (Pros)/Prox1 ensures neuronal differentiation by driving heterochromatin domain condensation and expansion. Intriguingly, in mitotically dividing Drosophila neural precursors, Pros is retained at H3K9me3+ pericentromeric heterochromatin regions of chromosomes via liquid-liquid phase separation (LLPS). During mitotic exit of neural precursors, mitotically retained Pros recruits and concentrates heterochromatin protein 1 (HP1) into phase-separated condensates and drives heterochromatin compaction. This establishes a transcriptionally repressive chromatin environment that guarantees cell-cycle exit and terminal neuronal differentiation. Importantly, mammalian Prox1 employs a similar “mitotic-implantation-ensured heterochromatin condensation” strategy to reinforce neuronal differentiation. Together, our results unveiled a new paradigm whereby mitotic implantation of a transcription factor via LLPS remodels H3K9me3+ heterochromatin and drives timely and irreversible terminal differentiation.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE136413 | GEO | 2019/12/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The control of transcriptional memory by stable mitotic bookmarking

Project description:To maintain cellular identities during development, gene expression profiles must be faithfully propagated through cell generations. The reestablishment of gene expression patterns upon mitotic exit is thought to be mediated, in part, by mitotic bookmarking by transcription factors (TF). However, the mechanisms and functions of TF mitotic bookmarking during early embryogenesis remain poorly understood. In this study, taking advantage of the naturally synchronized mitoses of Drosophila early embryos, we provide evidence that the pioneer-like transcription factor GAF acts as stable mitotic bookmarker during zygotic genome activation. We report that GAF remains associated to a large fraction of its interphase targets (37%). Mitotically-bound loci include cis-regulatory sequences of key developmental genes, with both active and repressive chromatin signatures. GAF mitotic targets are globally accessible during mitosis and a subset is also mitotically bookmarked via histone acetylation (H4K8ac). By monitoring the kinetics of transcriptional activation in living embryos, we provide evidence that GAF binding establishes competence for rapid activation upon mitotic exit.

2022-02-25 | GSE180812 | GEO

Prox1 inhibits axon outgrowth during central nervous system development

Project description:During central nervous system (CNS) development, proper and timely induction of axon elongation is critical for generating functional, mature neurons and neuronal networks. Despite the wealth of information on the action of extracellular cues, little is known about the intrinsic gene regulatory factors that control this developmental decision. Here we report the identification of Prox1, a homeobox transcription factor, as a key player in inhibiting axon elongation. Although Prox1 promotes acquisition of early neuronal identity and is expressed in nascent post-mitotic neurons, it is heavily down-regulated in the majority of terminally differentiated neurons, indicating a regulatory role in delaying axon outgrowth in newly formed neurons. Consistently, we show that Prox1 is sufficient to inhibit neurite extension in neuroblastoma cell lines. Furthermore, shRNA-mediated knock-down of Prox1 in Neuro2A cells induces the extension of neurites. More importantly, Prox1 overexpression suppresses axon elongation in primary neuronal cultures as well as in the developing mouse brain, while Prox1 knock-down promotes axon outgrowth. Mechanistically, RNA-Seq analysis reveals that Prox1 affects critical pathways for neuronal maturation and neurite extension. Interestingly, Prox1 strongly inhibits many components of Ca2+ signaling pathway, an important mediator of axon extension and neuronal maturation. In accordance, Prox1 represses Ca2+ entry upon KCl-mediated depolarization and reduce CREB phosphorylation. These observations suggest that Prox1 acts as a potent suppressor of axon elongation by inhibiting Ca2+ signaling pathway. This action may provide the appropriate time window for nascent neurons to find the correct position in the CNS prior to initiation of axon elongation.

2020-12-31 | GSE158904 | GEO

The Histone Variant H2A.W Defines Heterochromatin and Promotes Chromatin Condensation in Arabidopsis

Project description:Histone variants play crucial roles in gene expression, genome integrity and chromosome segregation. However, to what extent histone variants control chromatin architecture remains largely unknown. Here, we show that the previously uncharacterized histone variant H2A.W plays a crucial role in condensation of heterochromatin. Genome-wide profiling of all four types of H2A variants in Arabidopsis shows that H2A.W specifically associates with heterochromatin. H2A.W recruitment is independent of heterochromatic marks H3K9me2 and DNA methylation. Genetic interactions show that H2A.W acts in synergy with CMT3 mediated methylation to maintain genome integrity. In vitro, H2A.W enhances chromatin condensation through a higher propensity to make fiber-to-fiber interactions via its conserved C-terminal motif. In vivo, elimination of H2A.W causes decondensation of heterochromatin and conversely, ectopic expression of H2A.W promotes heterochromatin condensation. These results demonstrate that H2A.W plays critical roles in heterochromatin by promoting higher order chromatin condensation. Since similar H2A.W C-terminal motifs are present in other variant found in mammals and other organisms our findings impact our understanding of heterochromatin condensation in a wide variety of eukaryotic organisms. Two mRNA-seq samples, two bisulfite-seq samples, six ChIP-seq samples.

2014-07-05 | E-GEOD-50942 | biostudies-arrayexpress

ChIP-MS of HP1-beta (CBX1) and ubiquitylome of KAP1 (TRIM28) in mESCs

Project description:Heterochromatin binding protein HP1β plays an important role in chromatin organization and cell differentiation, however the underlying mechanisms remain unclear. Here, we generated HP1β-/- embryonic stem cells and observed reduced heterochromatin clustering and impaired differentiation. We found that during stem cell differentiation, HP1β is phosphorylated at serine 89 by CK2, which creates a binding site for the pluripotency regulator KAP1. This phosphorylation dependent sequestration of KAP1 in heterochromatin compartments causes a downregulation of pluripotency factors and triggers pluripotency exit. Accordingly, HP1β-/- and phospho-mutant cells exhibited impaired differentiation, while ubiquitination-deficient KAP1ΔRing cells had the opposite phenotype with enhanced differentiation. These results suggest that KAP1 regulates pluripotency via its ubiquitination activity. We propose that the formation of subnuclear membraneless heterochromatin compartments may serve as a dynamic reservoir to trap or release cellular factors. The sequestration of essential regulators defines a novel and active role of heterochromatin in gene regulation and represents a dynamic mode of remote control to regulate cellular processes like cell fate decisions.

2021-09-24 | PXD025053 | Pride

HOXC9-induced neuronal differentiation in human neuroblastoma BE(2)-C cells [Gene expression profiling]

Project description:Cell differentiation is an essential process of normal development by which a stem cell or progenitor cell becomes a post-mitotic, specialized cell with unique morphology and function. Also, it has long been recognized that differentiation is associated with a marked reduction in DNA damage response at the global level. The molecular basis for the coordination between cell cycle exit, acquirement of specialized structure and function, and attenuation of DNA damage response during differentiation is not well understood. We have conducted a genome-wide analysis of the HOXC9-induced neuronal differentiation program in human neuroblastoma cells. Gene expression profiling reveals that HOXC9-induced differentiation is associated with transcriptional regulation of 2,395 genes, which is characterized by global upregulation of neuronal genes and downregulation of cell cycle and DNA repair genes. Remarkably, genome-wide mapping demonstrates that HOXC9 occupies 40% of these genes, including a large number of genes involved in neuronal differentiation, cell cycle progression and DNA damage response. These findings suggest that HOXC9 directly activates and represses the transcription of distinct sets of genes to coordinate the cellular events characteristic of neuronal differentiation. Affymetrix microarray assays were performed according to the manufacturer's directions on total RNA isolated from three independent samples of BE(2)-C/Tet-Off/Myc-HOXC9 cells cultured in the presence or absence of doxycycline for 6 days.

2013-11-03 | E-GEOD-34420 | biostudies-arrayexpress

HOXC9-induced neuronal differentiation in human neuroblastoma BE(2)-C cells [ChIP-seq analysis]

Project description:Cell differentiation is an essential process of normal development by which a stem cell or progenitor cell becomes a post-mitotic, specialized cell with unique morphology and function. Also, it has long been recognized that differentiation is associated with a marked reduction in DNA damage response at the global level. The molecular basis for the coordination between cell cycle exit, acquirement of specialized structure and function, and attenuation of DNA damage response during differentiation is not well understood. We have conducted a genome-wide analysis of the HOXC9-induced neuronal differentiation program in human neuroblastoma cells. Gene expression profiling reveals that HOXC9-induced differentiation is associated with transcriptional regulation of 2,395 genes, which is characterized by global upregulation of neuronal genes and downregulation of cell cycle and DNA repair genes. Remarkably, genome-wide mapping demonstrates that HOXC9 occupies 40% of these genes, including a large number of genes involved in neuronal differentiation, cell cycle progression and DNA damage response. These findings suggest that HOXC9 directly activates and represses the transcription of distinct sets of genes to coordinate the cellular events characteristic of neuronal differentiation. Two independent preparations of BE(2)-C/Tet-Off/Myc-HOXC9 cells cultured in the absence of doxycycline for 6 days were used for chromatin immunoprecipitation (ChIP) against Myc-tagged HOXC9 and massively parallel sequencing by Illumina Genome Analyzer IIx.

2013-11-03 | E-GEOD-34419 | biostudies-arrayexpress

Effect of RFX3 or RFX4 knockdown on ventral telencephalic medial ganglionic eminence-like (MGE-like) neuronal precursors

Project description:RFX3 and RFX4 were defined as transcription factors (TFs) with enriched TF binding sites in cis-regulatory elements that are activated during the conversion of human embryonic stem cells (hESCs) into ventral telencephalic MGE-like patterned neuronal precursors. Therefore, we conducted CRISPRi-mediated knockdown of RFX3 or RFX4 and profiled changes in gene expression in MGE-like ventral telencephalic progenitors by RNA-seq. This analysis revealed that RFX3 and RFX4 play important roles in cortical interneuron development, specifically during the transition from mitotically cycling neuronal precursors into post mitotic neurons.

2024-04-18 | GSE239413 | GEO

Transcriptomics analysis of gene expression in Ddx3xb mutant injected with ddx3xbFL or ddx3xb△N

Project description:We show that liquid-liquid phase separation (LLPS)-mediated zebrafish Ddx3xb condensation facilitates MZT through promoting maternal mRNAs translation. Ddx3xb forms condensates via its N-terminal intrinsically disordered regions (IDRs), and the gradually increased ATP concentration after fertilization promotes its aggregation capability. Ddx3xb-deficiency decelerates the decay of maternal mRNAs and impedes zygotic genome activation, further leading to developmental defect. The phenotype in Ddx3xb-deficiency embryos can be efficiently rescued by condensed Ddx3xb, but not the Ddx3xb without LLPS ability. Mechanistically, the condensation of Ddx3xb is vital for its RNA helicase activity, which is critical for involved in promoting translation efficiency of maternal mRNAs through opening 5’ UTR structures during the MZT process. Our study demonstrates that the condensation of Ddx3xb promotes maternal mRNAs translation via its RNA unwinding activity and further facilitates MZT, highlighting the critical role of protein phase separation in translational control and animal early development.

2022-06-03 | GSE181503 | GEO

Transcriptomics analysis of gene expression in control and Ddx3xb knockout zebrafish embryos

2022-06-03 | GSE169166 | GEO

Transcriptomics analysis of gene expression in control and Ddx3xb knockdown zebrafish embryos

2022-06-03 | GSE169163 | GEO