Sustained TNF-α stimulation leads to transcriptional memory that greatly enhances signal sensitivity and robustness.

ABSTRACT: Transcriptional memory allows certain genes to respond to previously experienced signals more robustly. However, whether and how the key proinflammatory cytokine TNF-α mediates transcriptional memory are poorly understood. Using HEK293F cells as a model system, we report that sustained TNF-α stimulation induces transcriptional memory dependent on TET enzymes. The hypomethylated status of transcriptional regulatory regions can be inherited, facilitating NF-κB binding and more robust subsequent activation. A high initial methylation level and CpG density around κB sites are correlated with the functional potential of transcriptional memory modules. Interestingly, the CALCB gene, encoding the proven migraine therapeutic target CGRP, exhibits the best transcriptional memory. A neighboring prim

SUBMITTER: Zhao Z 

PROVIDER: S-EPMC7704108 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature