Transcription factor FOXM1 specifies the loading of chromatin DNA to extracellular vesicles

Abstract

Extracellular vesicle DNA (evDNA) acts as a potential mechanism for intercellular communication and possesses an important diagnostic value for multiple diseases. In this study, we have provided the first example that transcription factor determines the sources of evDNA from chromatin DNA. Transcription factor FOXM1 mediates the loading of specific chromatin DNA fragments into extracellular vesicles (EVs). Specifically, certain chromatin DNA fragments are specified by FOXM1 and form LC3-FOXM1-DNA vesicles in cytoplasm during autophagy. Then the cytoplasmic LC3-FOXM1-DNAs are transported to EVs probably through the process of an autophagy-MVB transport. We have confirmed that LC3-FOXM1-DNAs can be absorbed by recipient cells along with the released EVs and certain evDNA fragments integrate into the genome of recipient cells. This discovery provides an understanding for studying the sources and functions of evDNA and helps to expand its application in the future.