Embryonic stem cells differentiate into diverse cell types once they receive the appropriate signals. Until then, they are kept in the undifferentiated state by three transcriptional regulators called Oct4, Sox2, and Nanog. An important target of Oct4 and Sox2 is a gene called FGF4, and studies identified a DNA element that is required for both of these regulators to promote FGF4 transcription. The element is located at the 3' end of the sequence, beyond the coding region of the gene, and contains binding sites for Oct4 and Sox2 that are 3 nucleotides apart. When the element was mutated to increase the spacing between the sites, Oct4 and Sox2 could no longer stimulate transcription of the gene.
The level of Oct4 expression has strong effects on stem cell differentiation. When expressed at normal levels, Oct4 helps maintain the undifferentiated state. Overexpression of Oct4 by as little as 1.5-fold, however, causes stem cells to differentiate into mesoderm.
Bonus #1: What term best describes the DNA element that is required for Oct4 and Sox2 to promote FGF4 transcription?
Enhancer
Mediator
Promoter
TATA box
Bonus #2: Which of the following actions best explains how a minor change in Oct4 levels could lead to a big change in the differentiation state of cells?
Chromatin modification
Cooperative binding
Dimerization
Negative feedback