Bright/Arid3A Acts as a Barrier to Somatic Cell Reprogramming through Direct Regulation of Oct4, Sox2, and Nanog
| Autor: | Carol F. Webb, Catherine Rhee, Bum Kyu Lee, Troy D. Templeton, Melissa Popowski, He Li, Haley O. Tucker, Shari Orlanski, Cathrine A. Miner, Vishwanath R. Iyer, Joseph D. Dekker, Yehudit Bergman |
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| Rok vydání: | 2014 |
| Předmět: |
Homeobox protein NANOG
Octamer Transcription Factor-3 Somatic cell Lewis X Antigen Biology Biochemistry Cell Line Mice 03 medical and health sciences 0302 clinical medicine SOX2 Report Genetics Animals RNA Small Interfering Promoter Regions Genetic lcsh:QH301-705.5 Cellular Senescence 030304 developmental biology Homeodomain Proteins lcsh:R5-920 0303 health sciences SOXB1 Transcription Factors Nanog Homeobox Protein Cell Biology Cellular Reprogramming Embryonic stem cell Molecular biology DNA-Binding Proteins lcsh:Biology (General) 030220 oncology & carcinogenesis embryonic structures RNA Interference biological phenomena cell phenomena and immunity Transcriptome lcsh:Medicine (General) Cell aging Reprogramming Protein Binding Transcription Factors Developmental Biology |
| Zdroj: | Stem Cell Reports, Vol 2, Iss 1, Pp 26-35 (2014) Stem Cell Reports |
| ISSN: | 2213-6711 |
| DOI: | 10.1016/j.stemcr.2013.12.002 |
| Popis: | Summary We show here that singular loss of the Bright/Arid3A transcription factor leads to reprograming of mouse embryonic fibroblasts (MEFs) and enhancement of standard four-factor (4F) reprogramming. Bright-deficient MEFs bypass senescence and, under standard embryonic stem cell (ESC) culture conditions, spontaneously form clones that in vitro express pluripotency markers, differentiate to all germ lineages, and in vivo form teratomas and chimeric mice. We demonstrate that BRIGHT binds directly to the promoter/enhancer regions of Oct4, Sox2, and Nanog to contribute to their repression in both MEFs and ESCs. Thus, elimination of the BRIGHT barrier may provide an approach for somatic cell reprogramming. Highlights • Loss of Bright can alone reprogram or enhance conventional four-factor reprogramming • Bright directly represses Oct4, Sox2, and Nanog • Bright may function in somatic and embryonic stem cells to enforce differentiation Popowski et al. show that loss of the transcription factor Bright/Arid3A induces reprogramming in mouse embryonic fibroblasts (MEFs) and enhancement of standard four-factor reprograming. Bright-deficient reprogrammed cells express all pluripotency markers and are capable of forming teratomas and chimeric mice. Bright binds directly to the promoter/enhancer regions of Oct4, Sox2, and Nanog and contributes to their repression in both MEFs and embryonic stem cells. |
| Databáze: | OpenAIRE |
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