Back

FACT-mediated maintenance of chromatin integrity during transcription is essential for viability of mammalian stem cells

Goswami, I.; Sandlesh, P.; Stablewski, A.; Toshkov, I.; Magnitov, M.; Wang, J.; Gurova, K.

2021-06-22 systems biology
10.1101/2021.06.21.449309 bioRxiv
Show abstract

Preservation of nucleosomes during replication has been extensively studied, while the maintenance of nucleosomes during transcription has gotten less attention. The histone chaperone FACT is involved in transcription elongation, although whether it disassembles or assembles nucleosomes during this process is still unclear. We deleted the FACT subunit in adult mice to clarify the function of FACT in mammals. FACT loss was lethal due to the loss of the earliest progenitors in bone marrow and intestine, while mor differentiated cells were not affected. Using cells isolated from several tissues, we showed that FACT loss was lethal only for stem cells but not cells differentiated in vitro. FACT depletion led to increased chromatin accessibility in a transcription-dependent manner, suggesting that nucleosomes are lost during transcription in the absence of FACT. The most prominent response to the loss of nucleosomes was the activation of interferon signaling and the accumulation of immunocytes in sensitive organs. FACT maintained chromatin integrity during transcription in mammalian adult stem cells, suggesting that chromatin transcription in these cells is different from more differentiated cells.

Matching journals

The top 12 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.