Alternative Activation of Macrophages Is Accompanied by Chromatin Remodeling Associated with Lineage-Dependent DNA Shape Features Flanking PU.1 Motifs.
J Immunol
; 205(4): 1070-1083, 2020 08 15.
Article
em En
| MEDLINE
| ID: mdl-32661179
IL-4 activates macrophages to adopt distinct phenotypes associated with clearance of helminth infections and tissue repair, but the phenotype depends on the cellular lineage of these macrophages. The molecular basis of chromatin remodeling in response to IL-4 stimulation in tissue-resident and monocyte-derived macrophages is not understood. In this study, we find that IL-4 activation of different lineages of peritoneal macrophages in mice is accompanied by lineage-specific chromatin remodeling in regions enriched with binding motifs of the pioneer transcription factor PU.1. PU.1 motif is similarly associated with both tissue-resident and monocyte-derived IL-4-induced accessible regions but has different lineage-specific DNA shape features and predicted cofactors. Mutation studies based on natural genetic variation between C57BL/6 and BALB/c mouse strains indicate that accessibility of these IL-4-induced regions can be regulated through differences in DNA shape without direct disruption of PU.1 motifs. We propose a model whereby DNA shape features of stimulation-dependent genomic elements contribute to differences in the accessible chromatin landscape of alternatively activated macrophages on different genetic backgrounds that may contribute to phenotypic variations in immune responses.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Cromatina
/
Transativadores
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Proteínas Proto-Oncogênicas
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Macrófagos Peritoneais
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Montagem e Desmontagem da Cromatina
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article