The epigenetic pioneer EGR2 initiates DNA demethylation in differentiating monocytes at both stable and transient binding sites
| Autor: | Claudia Gebhard, Julia Minderjahn, Julia Wimmer, Michael Rehli, Sandra Schmidhofer, Dagmar Glatz, Johanna Raithel, Karina Mendes, Claudia Kiesewetter |
|---|---|
| Přispěvatelé: | Veritati - Repositório Institucional da Universidade Católica Portuguesa |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Immunoprecipitation Transcriptional regulatory elements Science Immunoblotting 610 Medizin General Physics and Astronomy Plasma protein binding Chromatin structure Mass Spectrometry Monocytes Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Humans RNA-Seq Epigenetics Binding site Transcription factor Cells Cultured Early Growth Response Protein 2 ddc:610 Binding Sites DNA methylation Multidisciplinary Chemistry Epigenetics in immune cells General Chemistry Chromatin Cell biology DNA Demethylation 030104 developmental biology DNA demethylation 030220 oncology & carcinogenesis Chromatin Immunoprecipitation Sequencing Protein Binding |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-021-21661-y |
| Popis: | The differentiation of human blood monocytes (MO), the post-mitotic precursors of macrophages (MAC) and dendritic cells (moDC), is accompanied by the active turnover of DNA methylation, but the extent, consequences and mechanisms of DNA methylation changes remain unclear. Here, we profile and compare epigenetic landscapes during IL-4/GM-CSF-driven MO differentiation across the genome and detect several thousand regions that are actively demethylated during culture, both with or without accompanying changes in chromatin accessibility or transcription factor (TF) binding. We further identify TF that are globally associated with DNA demethylation processes. While interferon regulatory factor 4 (IRF4) is found to control hallmark dendritic cell functions with less impact on DNA methylation, early growth response 2 (EGR2) proves essential for MO differentiation as well as DNA methylation turnover at its binding sites. We also show that ERG2 interacts with the 5mC hydroxylase TET2, and its consensus binding sequences show a characteristic DNA methylation footprint at demethylated sites with or without detectable protein binding. Our findings reveal an essential role for EGR2 as epigenetic pioneer in human MO and suggest that active DNA demethylation can be initiated by the TET2-recruiting TF both at stable and transient binding sites. DNA methylation turnover is an essential epigenetic process during development. Here, the authors look at the changes in DNA methylation during the differentiation of post-mitotic human monocytes (MO), and find that EGR2 interacts with TET2 and is required for DNA demethylation at its binding sites; revealing EGR2 as an epigenetic pioneer factor in human MO. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink