Enforcement of developmental lineage specificity by transcription factor Oct1
Author(s)Shen, Zuolian; Kang, Jinsuk; Shakya, Arvind; Tabaka, Marcin; Jarboe, Elke A; Regev, Aviv; Tantin, Dean; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Department of Biology
eLife Sciences Publications, Ltd
Shen, Zuolian et al. “Enforcement of Developmental Lineage Specificity by Transcription Factor Oct1.” eLife 6 (May 2017): e20937 © 2017 Shen et al.