Interferon stimulation creates chromatin marks and establishes transcriptional memory

Area of Science:

• Cellular Biology
• Epigenetics
• Immunology

Background:

• Epigenetic memory has been primarily associated with cell-autonomous processes.
• The role of external signals in establishing epigenetic memory in somatic cells is not well understood.

Purpose of the Study:

• To investigate if external signals, specifically interferon stimulation, can induce epigenetic memory in mammalian cells.
• To characterize the nature and inheritance of this transcriptional memory.

Main Methods:

• Fibroblast stimulation with Interferon-beta (IFNβ) and subsequent restimulation.
• Analysis of gene expression patterns (memory vs. non-memory ISGs).
• Investigation of molecular mechanisms including transcription factor binding, RNA polymerase II recruitment, and histone modifications (H3.3, H3K36me3).

Main Results:

• IFNβ stimulation establishes a transcriptional memory in fibroblasts, leading to faster and enhanced gene expression upon restimulation.
• This memory is inherited through multiple cell divisions and confers improved antiviral protection.
• Memory is linked to accelerated recruitment of RNA polymerase II and specific chromatin marks (H3.3, H3K36me3), not enhanced signaling pathways.

Conclusions:

• External signals can establish a form of epigenetic memory in mammalian cells.
• This epigenetic memory modifies the innate immune response, conferring lasting adaptive performance.
• The findings broaden the understanding of epigenetic memory beyond preprogrammed cellular processes.