CATaDa reveals global remodelling of chromatin accessibility during stem cell differentiation in vivo

Aughey, Gabriel; Estacio-Gómez, Alicia; Thomson, Jamie; Yin, Hang; Southall, Tony D.

doi:10.1101/189456

Cited by 4 publications

(14 citation statements)

References 60 publications

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“…Sensitivity to Dam methylation has previously been used as a tool to monitor chromatin structure in C. elegans , with a strong correlation between methylation and accessibility (Sha et al, 2010). More recently, tissue-specific Dam expression was used to determine chromatin accessibility from Drosophila neural and midgut lineages (Aughey et al, 2018). As discussed in this study, Dam methyltransferase failed to detect loci depleted for GATC when compared to assay for transposase-accessible chromatin (ATAC) or formaldehyde-assisted isolation of regulatory elements (FAIRE) data (Aughey et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…More recently, tissue-specific Dam expression was used to determine chromatin accessibility from Drosophila neural and midgut lineages (Aughey et al, 2018). As discussed in this study, Dam methyltransferase failed to detect loci depleted for GATC when compared to assay for transposase-accessible chromatin (ATAC) or formaldehyde-assisted isolation of regulatory elements (FAIRE) data (Aughey et al, 2018). The authors raised the limitations of the resolution achievable by Dam methylation, consistent with our analysis of GATC distribution in this organism and others (Figure S1A).…”

Section: Discussionmentioning

confidence: 99%

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MadID, a Versatile Approach to Map Protein-DNA Interactions, Highlights Telomere-Nuclear Envelope Contact Sites in Human Cells

Sobecki¹,

Souaid²,

Boulay³

et al. 2018

Cell Reports

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Summary Mapping the binding sites of DNA- or chromatin-interacting proteins is essential to understanding biological processes. DNA adenine methyltransferase identification (DamID) has emerged as a comprehensive method to map genome-wide occupancy of proteins of interest. A caveat of DamID is the specificity of Dam methyltransferase for GATC motifs that are not homogenously distributed in the genome. Here, we developed an optimized method named MadID, using proximity labeling of DNA by the methyltransferase M.EcoGII. M.EcoGII mediates N6-adenosine methylation in any DNA sequence context, resulting in deeper and unbiased coverage of the genome. We demonstrate, using m6A-specific immunoprecipitation and deep sequencing, that MadID is a robust method to identify protein-DNA interactions at the whole-genome level. Using MadID, we revealed contact sites between human telomeres, repetitive sequences devoid of GATC sites, and the nuclear envelope. Overall, MadID opens the way to identification of binding sites in genomic regions that were largely inaccessible.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MadID, a Versatile Approach to Map Protein-DNA Interactions, Highlights Telomere-Nuclear Envelope Contact Sites in Human Cells

Sobecki¹,

Souaid²,

Boulay³

et al. 2018

Cell Reports

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“…It is currently unclear whether this is due 401 to adult VNCs being absent from the profiling experiments, or differences between immature and fully 402 mature neurons, such as overall lower transcriptional activity in adults. We have previously shown 403 that global chromatin accessibility distribution in adult neurons is distinct from larval neurons 404 (Aughey et al, 2018), which may account for some of these differences. 405 Apart from the neurotransmitter synthesis genes, the chromatin accessibility of the subtypes, at a 406 given stage, is surprisingly similar, as demonstrated in embryos ( Figure 6).…”

Section: Transcriptional Profiling Of Neuronal Subtypes Across Develomentioning

confidence: 99%

“…Targeted DamID data analysis 565 Sequencing data for TaDa and CATaDa were mapped back to release 6.03 of the Drosophila genome 566 using a previously described pipelines (Aughey et al, 2018;Marshall and Brand, 2015 https://github.com/tonysouthall/Dam-RNA_POLII_analysis). Drosophila genome annotation release 570 6.11 was used, with 1% FDR and 0.2 log2 ratio thresholds.…”

Section: Targeted Damid (Tada) For Identification Of Acj6 and Ets65a-mentioning

confidence: 99%

Dynamic neurotransmitter specific transcription factor expression profiles duringDrosophiladevelopment

Estacio-Gómez

Hassan

Walmsley

et al. 2019

Preprint

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8The remarkable diversity of neurons in the nervous system is generated during development, when 9properties such as cell morphology, receptor profiles and neurotransmitter identities are specified. 10Neurotransmitters are essential for neuronal communication, and transcription factors are the key 11 determinants of neurotransmitter fate. In order to gain a greater understanding of neurotransmitter 12 specification we profiled the transcription state of cholinergic, GABAergic and glutamatergic neurons 13 in vivo at multiple developmental time points. We identified 86 differentially expressed transcription 14 factors that are uniquely enriched, or uniquely depleted, in a specific neurotransmitter subtype. Some 15 transcription factors show a similar profile across development, others only show enrichment or 16 depletion at specific developmental stages. Profiling of acj6 (cholinergic enriched) and Ets65A 17 (cholinergic depleted) binding sites in vivo reveals that they both directly bind the ChAT locus, in 18 addition to a wide spectrum of other key neuronal differentiation genes. Our data underlines that, 19 similar to C. elegans, there are no simple transcription factor codes for neurotransmitter type 20 specification, and provides a useful resource for studying the developmental basis of neurotransmitter 21 specification in Drosophila and other model systems. 22 enrichment of the GAL4-trapped genes (ChAT, Gad1 and VGlut) ( Figure S1) that provide subtype 126 specific expression for the TaDa experiments. 127 CATaDa profiling of chromatin accessibility (Aughey et al., 2018) reveals that, similar to RNA Pol II, 128 global chromatin accessibility does not vary greatly between cell types (Figure 2) but shows more 129 differences between developmental stages. Correspondingly, when examining regions of the genome 130 that display robust changes in chromatin accessibility (>10 RPM differences across 3 consecutive 131 GATC fragments) during embryo development, only 37 GATC fragments (13 individual peaks) are 132 identified, with 62% mapping to the loci of the three neurotransmitter synthesis genes (ChAT, Gad1 133

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“…However, underlying changes at the chromatin level are only just starting to be investigated. Changes in gene expression, chromatin accessibility and the 3D genome organisation all occur as neurons differentiate from progenitor cells [4–9]. Currently, little is known about the mechanisms underlying this transition and the molecular factors that coordinate it.…”

Section: Introductionmentioning

confidence: 99%

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

Hassan

Rodriguez

Heidmann

et al. 2020

Preprint

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AbstractThe condensin complex is essential for mitotic chromosome assembly and segregation during cell divisions, however, little is known about its function in post-mitotic, differentiated cells. Here we report a novel role for the condensin I subunit Cap-G in Drosophila neurons. We show that, despite not requiring condensin for mitotic chromosome compaction, post-mitotic neurons express Cap-G and that knockdown of Cap-G specifically in neurons (from their birth onwards) results in developmental arrest, behavioural defects, and dramatic gene expression changes. These include reduced expression of a subset of neuronal genes and aberrant expression of genes that are not normally expressed in the developing brain. Knockdown of Cap-G in more mature neurons also results in similar phenotypes but to a lesser degree. Furthermore, we see dynamic binding of Cap-G to chromatin at distinct loci in neural stem cells and differentiated neurons. Therefore, Cap-G is essential for proper gene expression in neurons and plays an important role during the early stages of neuronal development.

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CATaDa reveals global remodelling of chromatin accessibility during stem cell differentiation in vivo

Cited by 4 publications

References 60 publications

MadID, a Versatile Approach to Map Protein-DNA Interactions, Highlights Telomere-Nuclear Envelope Contact Sites in Human Cells

MadID, a Versatile Approach to Map Protein-DNA Interactions, Highlights Telomere-Nuclear Envelope Contact Sites in Human Cells

Dynamic neurotransmitter specific transcription factor expression profiles duringDrosophiladevelopment

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

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