Targeted DamID detects cell-type-specific histone modifications in intact tissues or organisms.

Histone modifications play a key role in regulating gene expression and cell fate during development and disease. Current methods for cell-type-specific genome-wide profiling of histone modifications require dissociation and isolation of cells and are not compatible with all tissue types. Here we ad...

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Main Authors: Jelle van den Ameele, Manuel Trauner, Eva Hörmanseder, Alex P A Donovan, Oriol Llorà-Batlle, Seth W Cheetham, Robert Krautz, Rebecca Yakob, Anna Malkowska, John B Gurdon, Andrea H Brand
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-03-01
Series:PLoS Biology
Online Access:https://doi.org/10.1371/journal.pbio.3002944
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author Jelle van den Ameele
Manuel Trauner
Eva Hörmanseder
Alex P A Donovan
Oriol Llorà-Batlle
Seth W Cheetham
Robert Krautz
Rebecca Yakob
Anna Malkowska
John B Gurdon
Andrea H Brand
author_facet Jelle van den Ameele
Manuel Trauner
Eva Hörmanseder
Alex P A Donovan
Oriol Llorà-Batlle
Seth W Cheetham
Robert Krautz
Rebecca Yakob
Anna Malkowska
John B Gurdon
Andrea H Brand
author_sort Jelle van den Ameele
collection DOAJ
description Histone modifications play a key role in regulating gene expression and cell fate during development and disease. Current methods for cell-type-specific genome-wide profiling of histone modifications require dissociation and isolation of cells and are not compatible with all tissue types. Here we adapt Targeted DamID (TaDa) to recognize specific histone marks, by fusing chromatin-binding proteins or single-chain antibodies to Dam, an Escherichia coli DNA adenine methylase. When combined with TaDa, this enables cell-type-specific chromatin profiling in intact tissues or organisms. We first profiled H3K4me3, H3K9ac, H3K27me3 and H4K20me1 in vivo in neural stem cells of the developing Drosophila brain. Next, we mapped cell-type-specific H3K4me3, H3K9ac and H4K20me1 distributions in the developing mouse brain. Finally, we injected RNA encoding DamID constructs into 1-cell stage Xenopus embryos to profile H3K4me3 distribution during gastrulation and neurulation. These results illustrate the versatility of TaDa to profile cell-type-specific histone marks throughout the genome in diverse model systems.
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spelling doaj-art-c2fbd2afec2141df9a87b2ae90cdc2862025-08-20T02:22:59ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852025-03-01233e300294410.1371/journal.pbio.3002944Targeted DamID detects cell-type-specific histone modifications in intact tissues or organisms.Jelle van den AmeeleManuel TraunerEva HörmansederAlex P A DonovanOriol Llorà-BatlleSeth W CheethamRobert KrautzRebecca YakobAnna MalkowskaJohn B GurdonAndrea H BrandHistone modifications play a key role in regulating gene expression and cell fate during development and disease. Current methods for cell-type-specific genome-wide profiling of histone modifications require dissociation and isolation of cells and are not compatible with all tissue types. Here we adapt Targeted DamID (TaDa) to recognize specific histone marks, by fusing chromatin-binding proteins or single-chain antibodies to Dam, an Escherichia coli DNA adenine methylase. When combined with TaDa, this enables cell-type-specific chromatin profiling in intact tissues or organisms. We first profiled H3K4me3, H3K9ac, H3K27me3 and H4K20me1 in vivo in neural stem cells of the developing Drosophila brain. Next, we mapped cell-type-specific H3K4me3, H3K9ac and H4K20me1 distributions in the developing mouse brain. Finally, we injected RNA encoding DamID constructs into 1-cell stage Xenopus embryos to profile H3K4me3 distribution during gastrulation and neurulation. These results illustrate the versatility of TaDa to profile cell-type-specific histone marks throughout the genome in diverse model systems.https://doi.org/10.1371/journal.pbio.3002944
spellingShingle Jelle van den Ameele
Manuel Trauner
Eva Hörmanseder
Alex P A Donovan
Oriol Llorà-Batlle
Seth W Cheetham
Robert Krautz
Rebecca Yakob
Anna Malkowska
John B Gurdon
Andrea H Brand
Targeted DamID detects cell-type-specific histone modifications in intact tissues or organisms.
PLoS Biology
title Targeted DamID detects cell-type-specific histone modifications in intact tissues or organisms.
title_full Targeted DamID detects cell-type-specific histone modifications in intact tissues or organisms.
title_fullStr Targeted DamID detects cell-type-specific histone modifications in intact tissues or organisms.
title_full_unstemmed Targeted DamID detects cell-type-specific histone modifications in intact tissues or organisms.
title_short Targeted DamID detects cell-type-specific histone modifications in intact tissues or organisms.
title_sort targeted damid detects cell type specific histone modifications in intact tissues or organisms
url https://doi.org/10.1371/journal.pbio.3002944
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