Condensin I subunit Cap-G is essential for proper gene expression during the maturation of post-mitotic neurons

Hassan, Amira; Rodriguez, Pablo Araguas; Heidmann, Stefan; Walmsley, Emma L; Aughey, Gabriel; Southall, Tony D.

doi:10.7554/elife.55159

Cited by 16 publications

(9 citation statements)

References 73 publications

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“…In almost all cases, these genes partially evaded the widespread transcriptional down-regulation that is inflicted by heat shock. A function in facilitating gene expression changes is consistent with the recently observed role of condensin in executing the transcriptional neuronal maturation programme in flies (Hassan et al, 2020).…”

Section: Discussionsupporting

confidence: 84%

A role for condensin in mediating transcriptional adaptation to environmental stimuli

et al. 2021

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Nuclear organisation shapes gene regulation; however, the principles by which three-dimensional genome architecture influences gene transcription are incompletely understood. Condensin is a key architectural chromatin constituent, best known for its role in mitotic chromosome condensation. Yet at least a subset of condensin is bound to DNA throughout the cell cycle. Studies in various organisms have reported roles for condensin in transcriptional regulation, but no unifying mechanism has emerged. Here, we use rapid conditional condensin depletion in the budding yeast Saccharomyces cerevisiae to study its role in transcriptional regulation. We observe a large number of small gene expression changes, enriched at genes located close to condensin-binding sites, consistent with a possible local effect of condensin on gene expression. Furthermore, nascent RNA sequencing reveals that transcriptional down-regulation in response to environmental stimuli, in particular to heat shock, is subdued without condensin. Our results underscore the multitude by which an architectural chromosome constituent can affect gene regulation and suggest that condensin facilitates transcriptional reprogramming as part of adaptation to environmental changes.

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Section: Discussionsupporting

confidence: 84%

A role for condensin in mediating transcriptional adaptation to environmental stimuli

et al. 2021

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“…Factors involved in the maintenance of neuronal transcriptomes during early neuronal maturation can have less severe phenotypes in fully differentiated neurons in which synapses have been formed (Southall et al , 2014 ; Hassan et al , 2020 ). This correlates with observed changes to the underlying chromatin landscape which is dynamic during differentiation and neuronal maturation (Marshall & Brand, 2017 ; Aughey et al , 2018 ).…”

Section: Resultsmentioning

confidence: 99%

NuRD‐independent Mi‐2 activity represses ectopic gene expression during neuronal maturation

et al. 2023

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During neuronal development, extensive changes to chromatin states occur to regulate lineage‐specific gene expression. The molecular factors underlying the repression of non‐neuronal genes in differentiated neurons are poorly characterised. The Mi2/NuRD complex is a multiprotein complex with nucleosome remodelling and histone deacetylase activity. Whilst NuRD has previously been implicated in the development of nervous system tissues, the precise nature of the gene expression programmes that it coordinates is ill‐defined. Furthermore, evidence from several species suggests that Mi‐2 may be incorporated into multiple complexes that may not possess histone deacetylase activity. We show that Mi‐2 activity is required for suppressing ectopic expression of germline genes in neurons independently of HDAC1/NuRD, whilst components of NuRD, including Mi‐2, regulate neural gene expression to ensure proper development of the larval nervous system. We find that Mi‐2 binding in the genome is dynamic during neuronal maturation, and Mi‐2‐mediated repression of ectopic gene expression is restricted to the early stages of neuronal development, indicating that Mi‐2/NuRD is required for establishing stable neuronal transcriptomes during the early stages of neuronal differentiation.

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“…Previous studies have shown that factors involved in the maintenance of neuronal transcriptomes during early neuronal maturation can have less severe phenotypes in fully differentiated neurons in which synapses have been formed (Hassan et al, 2020; Southall et al, 2014). This correlates with observed changes to the underlying chromatin landscape which is dynamic during differentiation and neuronal maturation (Aughey et al, 2018; Marshall and Brand, 2017).…”

Section: Resultsmentioning

confidence: 99%

“…It is possible to speculate that Mi-2/dMEC is required to establish a stable epigenetic state following recruitment by sequence specific transcription factor binding, after which these states are maintained by separate chromatin modifying proteins or complexes. We previously observed that neuron-appropriate gene expression programmes were maintained by Cap-G, a member of the condensin complex (Hassan et al, 2020). Similarly, with Mi-2 knockdown, less severe phenotypes – and fewer misregulated genes were apparent upon Cap-G depletion, indicating that multiple factors may act to maintain the neuronal transcriptome in early neuronal differentiation.…”

Section: Discussionmentioning

confidence: 99%

NuRD independent Mi-2 activity represses ectopic gene expression during neuronal maturation

Aughey

Forsberg

Grimes

et al. 2022

Preprint

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During neuronal development, extensive changes to chromatin states occur to regulate lineage-specific gene expression. The molecular factors underlying the repression of non-neuronal genes in differentiated neurons are poorly characterised. The Mi2/NuRD complex is a multiprotein complex with nucleosome remodelling and histone deacetylase activity. Whilst NuRD has previously been implicated in the development of nervous system tissues the precise nature of the gene expression programmes that it coordinates are ill-defined. Furthermore, evidence from several species suggests that Mi-2 may be incorporated into multiple complexes that may not possess histone deacetylase activity. Here, we show that Mi-2 activity is required for suppressing the ectopic expression of germline genes in neurons independently of HDAC1/NuRD, whilst components of the NuRD complex including Mi-2 regulate neural gene expression to ensure proper development of the larval nervous system. We find that Mi-2 binding in the genome is dynamic during neuronal maturation and Mi-2 mediated repression of ectopic gene expression is restricted to the early stages of neuronal development, indicating that Mi-2/NuRD is required for establishing stable neuronal transcriptomes during the early stages of neuronal differentiation.

show abstract

Condensin I subunit Cap-G is essential for proper gene expression during the maturation of post-mitotic neurons

Cited by 16 publications

References 73 publications

A role for condensin in mediating transcriptional adaptation to environmental stimuli

A role for condensin in mediating transcriptional adaptation to environmental stimuli

NuRD‐independent Mi‐2 activity represses ectopic gene expression during neuronal maturation

NuRD independent Mi-2 activity represses ectopic gene expression during neuronal maturation

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