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Rapid clearance of PcG histone modifications from Hox genes anticipates motor neuron differentiation: ChIP-chip

ABSTRACT: [original Title] Rapid and synchronous clearance of PcG histone modifications from Hox genes anticipates motor neuron differentiation. Hox genes are expressed in patterns that are spatially and temporally collinear with their chromosomal organization. This feature is an evolutionarily conserved hallmark of embryonic development, and in vertebrates it is critical, among others, for the specification of motor neuron subtypes and the wiring of sensory-motor circuits. We show here that the differentiation of motor neurons from stem cells is accompanied by a synchronous, domain-wide clearance of “repressive” Polycomb (PcG)-dependent histone methylation from Hox gene chromatin domains. These findings argue against the idea, advanced recently, that the collinear dynamics of Hox gene expression invariably reflects the progressive clearance of repressive chromatin modifications. The rapid establishment of stable chromatin domains in response to a transient patterning signal likely serves as a molecular correlate of enduring rostro-caudal neural identity, which underlies the specification of postmitotic motor neuron subtype diversity and neuronal circuit assembly.

ORGANISM(S): Mus musculus

PROVIDER: GSE19447 | GEO | 2013/07/04

SECONDARY ACCESSION(S): PRJNA123693

REPOSITORIES: GEO

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Rapid clearance of PcG histone modifications from Hox genes anticipates motor neuron differentiation: ChIP-chip

Project description:[original Title] Rapid and synchronous clearance of PcG histone modifications from Hox genes anticipates motor neuron differentiation. Hox genes are expressed in patterns that are spatially and temporally collinear with their chromosomal organization. This feature is an evolutionarily conserved hallmark of embryonic development, and in vertebrates it is critical, among others, for the specification of motor neuron subtypes and the wiring of sensory-motor circuits. We show here that the differentiation of motor neurons from stem cells is accompanied by a synchronous, domain-wide clearance of M-bM-^@M-^\repressiveM-bM-^@M-^] Polycomb (PcG)-dependent histone methylation from Hox gene chromatin domains. These findings argue against the idea, advanced recently, that the collinear dynamics of Hox gene expression invariably reflects the progressive clearance of repressive chromatin modifications. The rapid establishment of stable chromatin domains in response to a transient patterning signal likely serves as a molecular correlate of enduring rostro-caudal neural identity, which underlies the specification of postmitotic motor neuron subtype diversity and neuronal circuit assembly. The differentiation of ventral motor neurons is induced by treating embryonic stem cell cultures with retinoic acid and hedgehog agonist. Here, ChIP-chip using a custom Agilent array is used to profile the occupancy of H3K27me3, H3K4me3, and H3K79me2 at various defined stages during the differentiation process.

2013-07-04 | E-GEOD-19447 | biostudies-arrayexpress

Project description:Rapid and synchronous clearance of PcG histone modifications from Hox genes anticipates motor neuron differentiation

| PRJNA120309 | ENA

Mus musculus

Project description:Rapid clearance of PcG histone modifications from Hox genes anticipates motor neuron differentiation: ChIP-chip

| PRJNA123693 | ENA

Analysis of gene expression along the Hoxa cluster at five time-points during motor neuron differentiation

Project description:To dissect the significance underlying the delay between Hox transcription and translation, we profiled global Hox gene expression using an in vitro ESC-derived motor neuron differentiation system

2017-03-01 | GSE91080 | GEO

Induced Cdx2 binding in progenitor motor neurons and its effect on H3K27me3 chromatin domains [Affymetrix]

Project description:We aim to understand the role that Cdx2 plays in specifying the rostro-caudal identity of differentiating motor neurons. We find that expressing Cdx2 in combination with FGF signaling is sufficient to produce motor neurons with a more caudal identity. ChIP-seq analysis of Cdx2 finds that it binds extensively throughout the Hox regions in progenitor motor neurons. Analysis of polycomb-associated chromatin over Hox regions in the subsequently generated motor neurons finds that Cdx2 binding corresponds to chromatin domains encompassing de-repressed caudal Hox genes. These results suggest a direct role for Cdx2 in specifying caudal motor neuron identity. Expression studies: Affymetrix arrays are used to profile gene expression in ES cells, RA/Hh-derived Day 5 motor neurons, and RA/Hh-derived motor neurons that have also been exposed to Dox (to activate iCdx2) and FGF.

2013-07-04 | E-GEOD-39422 | biostudies-arrayexpress

Induced Cdx2 binding in progenitor motor neurons and its effect on H3K27me3 chromatin domains [ChIP-Seq]

2013-07-04 | GSE39433 | GEO

Induced Cdx2 binding in progenitor motor neurons and its effect on H3K27me3 chromatin domains [Affymetrix]

2013-07-04 | GSE39422 | GEO

Dynamic extrinsic pacing of the HOX clock in human axial progenitors control motor neuron subtype specification

Project description:Dynamic extrinsic pacing of the HOX clock in human axial progenitors control motor neuron subtype specification

| PRJNA642885 | ENA

Dynamic extrinsic pacing of the HOX clock in human axial progenitors control motor neuron subtype specification

Project description:Rostro-caudal patterning of vertebrates depends on the temporally progressive activation of HOX genes within axial stem cells that fuel axial embryo elongation. Whether HOX genes sequential activation, the “HOX clock”, is paced by intrinsic chromatin-based timing mechanisms or by temporal changes in extrinsic cues remains unclear. Here, we studied HOX clock pacing in human pluripotent stem cells differentiating into spinal cord motor neuron subtypes which are progenies of axial progenitors. We show that the progressive activation of caudal HOX genes is controlled by a dynamic increase in FGF signaling. Blocking FGF pathway stalled induction of HOX genes, while precocious increase in FGF alone, or with GDF11 ligand, accelerated the HOX clock. Cells differentiated under accelerated HOX induction generated appropriate posterior motor neuron subtypes found along the human embryonic spinal cord. The HOX clock is thus dynamically paced by exposure parameters to secreted cues. Its manipulation by extrinsic factors alleviates temporal requirements to provide unprecedented synchronized access to human cells of multiple, defined, rostro-caudal identities for basic and translational applications.

2021-03-02 | GSE153519 | GEO

PRC1 Sustains the Memory of Neuronal Fate Independent of PRC2 Function

Project description:Polycomb repressive complexes (PRCs) 1 and 2 maintain stable cellular memories of early developmental patterning programs by establishing heritable patterns of gene repression. PRCs repress transcription through histone modifications and chromatin compaction, but their roles in neuronal subtype diversification are poorly defined. We unexpectedly found that PRC2 is dispensable to preserve the Hox transcription factor-dependent positional identity of spinal motor neurons (MNs), while PRC1 is essential for the specification of segmentally-restricted subtypes. Mutation of the core PRC1 component Ring1 leads to increased chromatin accessibility and ectopic expression of a broad variety of fates determinants, including Hox genes, while general features of MNs are maintained. Loss of MN subtype-specific fates in Ring1 mutants is due to the suppression of Hox networks by derepressed caudal Hox genes. These results indicate that PRC1 can function independently of de novo PRC2-dependent methylation to maintain chromatin topology and transcriptional identity at the time of differentiation.

2022-01-10 | GSE175503 | GEO

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