Alternative Splicing Switch

Adapted from Cell doi:10.1016/j.cell.2011.08.023

Alternative splicing (AS) is a key process underlying the expansion of proteomic diversity and the regulation of gene expression. Scientists from Canada and USA identified an evolutionarily conserved embryonic stem cell (ESC)-specific AS event that changes the DNA-binding preference of the forkhead family transcription factor FOXP1. An ESC-specific splicing switch in FOXP1 transcripts produces the FOXP1-ES isoform. FOXP1-ES has distinct DNA-binding properties compared to the canonical FOXP1 isoform. FOXP1-ES stimulates key pluripotency genes and represses many differentiation genes. FOXP1-ES is required for ESC pluripotency and efficient induced pluripotent stem cells (iPSC) reprogramming.

These results reveal a pivotal role for an AS event in the regulation of pluripotency through the control of critical ESC-specific transcriptional programs.

The findings are published in the recent issue of Cell