Enforcement of developmental lineage specificity by transcription factor Oct1
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Shen, Zuolian; Kang, Jinsuk; Shakya, Arvind; Tabaka, Marcin; Jarboe, Elke A; Regev, Aviv; Tantin, Dean; ... Show more Show less![Thumbnail](/bitstream/handle/1721.1/111796/elife-20937-v2.pdf.jpg?sequence=7&isAllowed=y)
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Embryonic stem cells co-express Oct4 and Oct1, a related protein with similar DNA-binding specificity. To study the role of Oct1 in ESC pluripotency and transcriptional control, we constructed germline and inducible-conditional Oct1-deficient ESC lines. ESCs lacking Oct1 show normal appearance, self-renewal and growth but manifest defects upon differentiation. They fail to form beating cardiomyocytes, generate neurons poorly, form small, poorly differentiated teratomas, and cannot generate chimeric mice. Upon RA-mediated differentiation, Oct1-deficient cells induce lineage-appropriate developmentally poised genes poorly while lineage-inappropriate genes, including extra-embryonic genes, are aberrantly expressed. In ESCs, Oct1 co-occupies a specific set of targets with Oct4, but does not occupy differentially expressed developmental targets. Instead, Oct1 occupies these targets as cells differentiate and Oct4 declines. These results identify a dynamic interplay between Oct1 and Oct4, in particular during the critical window immediately after loss of pluripotency when cells make the earliest developmental fate decisions.
Date issued
2017-05Department
Massachusetts Institute of Technology. Department of BiologyJournal
eLife
Publisher
eLife Sciences Publications, Ltd
Citation
Shen, Zuolian et al. “Enforcement of Developmental Lineage Specificity by Transcription Factor Oct1.” eLife 6 (May 2017): e20937 © 2017 Shen et al.
ISSN
2050-084X