How is a multiple cellular organism being regulated to generate different cell types has been an intriguing and fundamental question for developmental biology. One explanation is that the expression of certain transcription factors at defined developmental stages can drive the formation of new cell types. Yet studies have shown that a great proportion of genes are ubiquitously expressed. How are these ubiquitously expressed genes being regulated to participate in cell-type-specific functions remains obscure.
In this work, Prof. Xiu-Jie Wang’s group from the Institute of Genetics and Developmental Biology and Prof. Qi Zhou’s group from the Institute of Zoology, both belonging to Chinese Academy of Sciences, discovered that ubiquitously expressed genes could acquire cell-type-specific functions by producing new cell-type-specific transcript isoforms via alternative promoter usage. They identified 110 mouse embryonic stem cell (mESC) specifically expressed transcripts with cell-type-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 some SATS isoforms 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 research was supported by grants from National Basic Research Program of China, CAS Strategic Priority Research Program Grants on Stem Cell and Regeneration Medicine, and National Natural Science Foundation of China.
Figure: Key pluripotency factors regulate ubiquitously expressed genes to produce SATS isoforms in mESCs via mESC-specific promoters.
