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DNA methylation signatures reveal that distinct combinations of transcription factors specify human immune cell epigenetic identity by Roshni Roy; Senthilkumar Ramamoorthy; Benjamin D. Shapiro; Mary Kaileh; Dena Hernandez; Dimitra Sarantopoulou; Sampath Arepalli; Sören Boller; Amit Singh; Arsun Bektas; Jaekwan Kim; Ann Zenobia Moore; Toshiko Tanaka; Julia McKelvey; Linda Zukley; Cuong Nguyen; Tonya Wallace; Christopher Dunn; Robert Wersto; William Wood; Yulan Piao; Kevin G. Becker; Christopher Coletta; Supriyo De; Jyoti Misra Sen; Alexis Battle; Nan-ping Weng; Rudolf Grosschedl; Luigi Ferrucci; Ranjan Sen is a Immunology and Microbiology article available to read on EtoBox.

What is DNA methylation signatures reveal that distinct combinations of transcription factors specify human immune cell epigenetic identity about?

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.

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Author

Roshni Roy; Senthilkumar Ramamoorthy; Benjamin D. Shapiro; Mary Kaileh; Dena Hernandez; Dimitra Sarantopoulou; Sampath Arepalli; Sören Boller; Amit Singh; Arsun Bektas; Jaekwan Kim; Ann Zenobia Moore; Toshiko Tanaka; Julia McKelvey; Linda Zukley; Cuong Nguyen; Tonya Wallace; Christopher Dunn; Robert Wersto; William Wood; Yulan Piao; Kevin G. Becker; Christopher Coletta; Supriyo De; Jyoti Misra Sen; Alexis Battle; Nan-ping Weng; Rudolf Grosschedl; Luigi Ferrucci; Ranjan Sen

Publisher

Elsevier BV

Published

2021

Language

EN

Field

Immunology and Microbiology (Life Sciences)