DNA methylation signatures reveal that distinct combinations of transcription factors specify human immune cell epigenetic identity
| Autor: | Sören Boller, Tonya Wallace, Christopher E. Coletta, Dimitra Sarantopoulou, Julia McKelvey, Yulan Piao, Luigi Ferrucci, Cuong Q. Nguyen, Sampath Arepalli, Benjamin D. Shapiro, Christopher A. Dunn, Mary Kaileh, Ranjan Sen, Dena G. Hernandez, Linda Zukley, Nan-ping Weng, Arsun Bektas, Alexis Battle, Roshni Roy, Ann Zenobia Moore, Senthilkumar Ramamoorthy, Supriyo De, Toshiko Tanaka, Kevin G. Becker, Rudolf Grosschedl, Amit Singh, William H. Wood, Jaekwan Kim, Jyoti Misra Sen, Robert P. Wersto |
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| Rok vydání: | 2022 |
| Předmět: |
Epigenomics
Genetics Cell type Immunology Immunity DNA Methylation Immune dysregulation Biology medicine.disease_cause Article Epigenesis Genetic Immune system Infectious Diseases Gene Expression Regulation Immune System DNA methylation medicine Humans Immunology and Allergy Epigenetics Transcriptome Transcription factor Reprogramming Transcription Factors |
| Zdroj: | Immunity |
| ISSN: | 1074-7613 |
| Popis: | Epigenetic reprogramming underlies specification of immune cell lineages, but patterns that uniquely define immune cell types and the mechanisms by which they are established remain unclear. Here, we identified lineage-specific DNA methylation signatures of six immune cell types from human peripheral blood and determined their relationship to other epigenetic and transcriptomic patterns. Sites of lineage-specific hypomethylation were associated with distinct combinations of transcription factors in each cell type. By contrast, sites of lineage-specific hypermethylation were restricted mostly to adaptive immune cells. PU.1 binding sites were associated with lineage-specific hypo- and hypermethylation in different cell types, suggesting that it regulates DNA methylation in a context-dependent manner. These observations indicate that innate and adaptive immune lineages are specified by distinct epigenetic mechanisms via combinatorial and context-dependent use of key transcription factors. The cell-specific epigenomics and transcriptional patterns identified serve as a foundation for future studies on immune dysregulation in diseases and aging. |
| Databáze: | OpenAIRE |
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