Core promoter recognition complex changes accompany liver development

Abstract

Recent studies of several key developmental transitions have brought into question the long held view of the basal transcriptional apparatus as ubiquitous and invariant. In an effort to better understand the role of core promoter recognition and coactivator complex switching in cellular differentiation, we have examined changes in transcription factor IID (TFIID) and cofactor required for Sp1 activation/Mediator during mouse liver development. Here we show that the differentiation of fetal liver progenitors to adult hepatocytes involves a wholesale depletion of canonical cofactor required for Sp1 activation/Mediator and TFIID complexes at both the RNA and protein level, and that this alteration likely involves silencing of transcription factor promoters as well as protein degradation. It will be intriguing for future studies to determine if a novel and as yet unknown core promoter recognition complex takes the place of TFIID in adult hepatocytes and to uncover the mechanisms that down-regulate TFIID during this critical developmental transition.TATA box-binding protein-associated factor | hepatoblast | hepatogenesis T he precise and orderly differentiation of embryonic progenitors to committed adult cell types requires exquisite spatial and temporal control of gene expression. Until recently, the dynamic changes in transcriptional output that accompany developmental transitions were assumed to depend exclusively on regulatory DNA and its associated sequence-specific activators and repressors, whereas core promoter recognition, coactivator, and chromatin modifier complexes were generally taken to be ubiquitous and invariant from one cell type to the next. Indeed, these so-called core factors are highly conserved from yeast to man (1). However, recent evidence suggests that several key developmental transitions are accompanied by, and actually require, dramatic changes in components of this general machinery including transcription factor IID (TFIID) composed of the TATA box-binding protein (TBP) and its associated factors (TAFs), the cofactor required for Sp1 activation/Mediator (CRSP/Med) complex, and the Brg1/Brm-associated factor (BAF) complex (for review, see 2).The first evidence that some cell types may contain alterations of the general machinery came with the identification of germcell-specific TFIID subcomplexes in which key subunits are replaced by paralogous components. Initially oogenesis and spermatogenesis were found to require an altered TFIID in which paralogous TAF4b replaces the canonical TAF4 (3, 4). Later spermatocytes were found to also express paralogous TAF7L that may cooperate with TBP and

The General Transcription Factor TAF7 Is Essential for Embryonic Development but Not Essential for the Survival or Differentiation of Mature T Cells

“…8B). Thus, the maturation of T cells is not accompanied by a change in TFIID composition, as has been reported in other systems (12,11). …”

“…For example, it has been reported that during the differentiation of myoblasts to myocytes, multiple TFIID components, including TBP, are lost (12). Similarly, the requirement for TAFs changes during hepatocyte development (11). Cell type-specific requirements for TAFs, such as TAF10, have been reported in other systems (20,25,35).…”

TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis

“…We performed MS analysis of human and mouse cultured erythroid progenitor cells at an immature stage (proerythroblasts) and upon differentiation, which revealed that most of the TFIID and SAGA subunits are present in these complexes at all stages analyzed. Our data exclude the possibility of a total rearrangement of the TFIID or SAGA complexes in this differentiation system, in contrast to what was reported for TFIID during liver hepatocyte (64) or myoblast (65) differentiation. Nevertheless, during differentiation we observed a dynamic reorganization of some TFIID and SAGA subunits, usually affecting those that have paralogues, such as TAF4/TAF4b, TAF9/TAF9b, GCN5/PCAF, and ATXN7/ATXN7L1/ATXN7L2, without affecting the core structure of these complexes.…”

The Mediator complex: a central integrator of transcription

“…In support of this, it appears that the subunit composition of Mediator is simplified in differentiated cells 13,14 . Whereas the phenomenon of simplified subunit composition in differentiated cells is best defined for the multi-subunit transcription factor IID (TFIID) complex 15 , smaller Mediator complexes with fewer than the typical 26 subunits would also likely adopt more specialized functions.…”