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Publication : Enforcement of developmental lineage specificity by transcription factor Oct1.

First Author  Shen Z Year  2017
Journal  Elife Volume  6
PubMed ID  28537559 Mgi Jnum  J:259896
Mgi Id  MGI:6141750 Doi  10.7554/eLife.20937
Citation  Shen Z, et al. (2017) Enforcement of developmental lineage specificity by transcription factor Oct1. Elife 6:e20937
abstractText  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.
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