Cell Identity Establishment and Maintenance: A Role for the Core Promoter Machinery

In vitro differentiation of mouse embryonic stem cells (ESCs) to oligodendrocytes (OLs). Different time points along the process (day -7 to day 26) are captured by phase-contrast microscopy. EBs: embryoid bodies, NPCs: neural progenitor cells, OPCs: oligodendrocyte progenitors.
Basal transcription factors like TFIID, also known as general transcription factors, are proteins that can bind gene promoters and recruit RNA polymerase II to allow transcription initiation. Recent lines of evidence using terminally differentiated cells indicate that these factors are not that general after all. Instead, specialized core promoter complexes exist that cooperate with sequence-specific transcription factors to establish and maintain cell identity.

TFIID is composed of the TATA-binding protein TBP and several TBP-associated factors (TAFs). We have recently shown that a non-canonical TAF variant (TAF9B) regulates gene expression during murine motor neuron development. We are now investigating the role of TAF9B in the mouse adult brain, where TAF9B is highly and widely expressed across different regions. Preliminary data by others and us indicate that Taf9b expression is enriched in oligodendrocyte progenitor cells and newly formed oligodendrocytes compared to neurons and other glial cells. We are currently assessing the functional significance of such enrichment using both in vitro and in vivo models of oligodendrogenesis in wild type and Taf9b-/- backgrounds. The project is in collaboration with Aaron Friedman, a graduate student in the Daniela Kaufer lab at UC Berkeley.

Claudia Cattoglio