How do different cell types acquire their specific identities and functions is a fundamental question of biology. Previously significant efforts have been devoted to search for cell‐type‐specifically expressed genes, especially transcription factors, yet how do ubiquitously expressed genes participate in the formation or maintenance of cell‐type‐specific features remains largely unknown. Here, we have identified 110 mouse embryonic stem cell (mESC) specifically expressed transcripts with cell‐stage‐specific alternative transcription start sites (SATS isoforms) from 104 ubiquitously expressed genes, majority of which have active epigenetic modification‐ or stem cell‐related functions. These SATS isoforms are specifically expressed in mESCs, and tend to be transcriptionally regulated by key pluripotency factors through direct promoter binding. Knocking down the SATS isoforms of Nmnat2 or Usp7 leads to differentiation‐related phenotype in mESCs. These results demonstrate that cell‐type‐specific transcription factors are capable to produce cell‐type‐specific transcripts with alternative transcription start sites from ubiquitously expressed genes, which confer ubiquitously expressed genes novel functions involved in the establishment or maintenance of cell‐type‐specific features.
This study shows that ubiquitously expressed genes can be involved in the establishment or maintenance of cell‐type‐specific features via producing cell‐type‐specific transcripts with alternative transcription start sites, some of which are regulated by cell‐type‐specific transcription factors.
Some ubiquitously expressed genes produce transcripts with stage‐specific alternative transcription start sites (SATS) in mESCs.
Key pluripotency factors regulate the expression of some SATS isoforms.
In mESCs, SATS isoforms are required for the maintenance of pluripotency.
EMBO Reports (2016) 17: 1304–1313
- Received October 1, 2015.
- Revision received June 28, 2016.
- Accepted June 28, 2016.
- © 2016 The Authors
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