TOBF1 modulates mouse embryonic stem cell fate through regulating alternative splicing of pluripotency genes

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  • Meghali Aich
  • Asgar Hussain Ansari
  • Ding, Li
  • Vytautas Iesmantavicius
  • Deepanjan Paul
  • Choudhary, Chuna Ram
  • Souvik Maiti
  • Frank Buchholz
  • Debojyoti Chakraborty

Embryonic stem cells (ESCs) can undergo lineage-specific differentiation, giving rise to different cell types that constitute an organism. Although roles of transcription factors and chromatin modifiers in these cells have been described, how the alternative splicing (AS) machinery regulates their expression has not been sufficiently explored. Here, we show that the long non-coding RNA (lncRNA)-associated protein TOBF1 modulates the AS of transcripts necessary for maintaining stem cell identity in mouse ESCs. Among the genes affected is serine/arginine splicing factor 1 (SRSF1), whose AS leads to global changes in splicing and expression of a large number of downstream genes involved in the maintenance of ESC pluripotency. By overlaying information derived from TOBF1 chromatin occupancy, the distribution of its pluripotency-associated OCT-SOX binding motifs, and transcripts undergoing differential expression and AS upon its knockout, we describe local nuclear territories where these distinct events converge. Collectively, these contribute to the maintenance of mouse ESC identity.

Original languageEnglish
Article number113177
JournalCell Reports
Volume42
Issue number10
Number of pages22
ISSN2211-1247
DOIs
Publication statusPublished - 2023

Bibliographical note

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© 2023 The Authors

    Research areas

  • alternative splicing, CP: Stem cell research, CRISPR interference, mESCs, OCT-SOX, Panct1, pluripotency, SRSF1, TOBF1

ID: 369122589