Participation of the TBP-associated factors (TAFs) in cell differentiation

The understanding of the mechanisms that regulate gene expression to establish differentiation programs and determine cell lineages, is one of the major challenges in Developmental Biology. Besides the participation of tissue-specific transcription factors and epigenetic processes, the role of general transcription factors has been ignored. Only in recent years, there have been scarce studies that address this issue. Here, we review the studies on the biological activity of some TATA-box binding protein (TBP)-associated factors (TAFs) during the proliferation of stem/progenitor cells and their involvement in cell differentiation. Particularly, the accumulated evidence suggests that TAF4, TAF4b, TAF7L, TAF8, TAF9, and TAF10, among others, participate in nervous system development, adipogenesis, myogenesis, and epidermal differentiation; while TAF1, TAF7, TAF15 may be involved in the regulation of stem cell proliferative abilities and cell cycle progression. On the other hand, evidence suggests that TBP variants such as TBPL1 and TBPL2 might be regulating some developmental processes such as germ cell maturation and differentiation, myogenesis, or ventral specification during development. Our analysis shows that it is necessary to study in greater depth the biological function of these factors and its participation in the assembly of specific transcription complexes that contribute to the differential gene expression that gives rise to the great diversity of cell types existing in an organism. The understanding of TAFs' regulation might lead to the development of new therapies for patients which suffer from mutations, alterations, and dysregulation of these essential elements of the transcriptional machinery. During long time, the TATA-box binding protein (TBP) and the TBP-associated factors (TAFs) that constitute the TFIID complex, were only considered as General Transcription Factors essential to recruit RNA polymerase II to the promoters of expressed genes. Now, accumulated evidence shows that some TAFs and TBP variants are crucial to determine cell type-specific gene expression, as well as elements that drive and modulate gene expression during cell cycle. While canonical TFIID complexes containing 13 to 14 different TAFs participate in transcription of 20%-30% of human genes, transcription of class I and class II genes requires TFIID complexes composed of TBP and specific TAFs as occurs for SOX2 and KLF4 or OCT4 and NANOG, respectively. Also, other members of the TBP family such as TBPL1 and TBPL2 are involved on the proper establishment of cell lineages and specialized phenotypes as occurs in female germ cell differentiation and meiotic maturation.image