TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis

Abstract

The ordered assembly of a functional preinitiation complex (PIC), composed of general transcription factors (GTFs), is a prerequisite for the transcription of protein-coding genes by RNA polymerase II. TFIID, comprised of the TATA binding protein (TBP) and 13 TBP-associated factors (TAFs), is the GTF that is thought to recognize the promoter sequences allowing site-specific PIC assembly. Transcriptional cofactors, such as SAGA, are also necessary for tightly regulated transcription initiation. The contribution of the two TAF10-containing complexes (TFIID, SAGA) to erythropoiesis remains elusive. By ablating TAF10 specifically in erythroid cells in vivo, we observed a differentiation block accompanied by deregulated GATA1 target genes, including Gata1 itself, suggesting functional cross talk between GATA1 and TAF10. Additionally, we analyzed by mass spectrometry the composition of TFIID and SAGA complexes in mouse and human cells and found that their global integrity is maintained, with minor changes, during erythroid cell differentiation and development. In agreement with our functional data, we show that TAF10 interacts directly with GATA1 and that TAF10 is enriched on the GATA1 locus in human fetal erythroid cells. Thus, our findings demonstrate a cross talk between canonical TFIID and SAGA complexes and cell-specific transcription activators during development and differentiation. Initiation of RNA polymerase II (RNA pol II) transcription in eukaryotes is a process involving the stepwise recruitment and assembly of the preinitiation complex (PIC) at the core promoter of a transcriptional unit. Transcription factor TFIID, comprised of the TATA binding protein (TBP) and a series of TBP-associated factors (TAFs), is the general transcription factor (GTF) that, by recognizing the promoter sequences and surrounding chromatin marks, allows the site-specific assembly of the PIC (see reference 1 and references therein). Binding of the TFIID complex is aided by TFIIA and is followed by the remainder of the general transcription machinery, including TFIIB, RNA pol II/TFIIF, TFIIE, and TFIIH complexes. Additional cofactors, including the Mediator complex, histone modifiers, and chromatin remodelers, facilitate the communication between gene-specific transcription factors and the general transcription machinery.The TFIID complex binds not only to TATA box-containing promoters but also to TATA-less promoters, and this led to the idea that TAFs could provide TFIID with additional functional features (2, 3). Indeed, 9 out of 13 TAFs contain a histone fold domain (HFD) (4) favoring the formation of TAF heterodimers. For instance, the TAF6-TAF9 heterodimer has been found to bind promoter elements downstream of the TATA box (5-7) and is a direct target of transcriptional activators (8, 9). Moreover, it has been shown that TAF knockouts (KOs) and in vitro TAF-knockdown experiments result in both the down-and upregulated expression of subsets of genes (10, 11). All these results together suggest that TFIID is a highly flexible r...

GATA1-Deficient Dendritic Cells Display Impaired CCL21-Dependent Migration toward Lymph Nodes Due to Reduced Levels of Polysialic Acid

“…A different set of enriched motifs was identified when taking downregulated genes, which included motifs for TAL1, bZIP, Maz (ZF), ETS, and TBP. Transcription factors recognizing these motifs have been reported to interact directly or to cooperate with GATA1 or other GATA transcription factors (55)(56)(57)(58)(59)(60)(61)(62)(63)(64). GO term enrichment analyses revealed a number of specific processes that were affected in R26R-RG|Gata1-KO DC DCs upon LPS stimulation.…”

The TAF10-containing TFIID and SAGA transcriptional complexes are dispensable for early somitogenesis in the mouse embryo

“…The difference of sensitivity to the loss of Taf10 in the mesoderm is the first to be observed in vivo, in an embryonic lineage. A tempting speculation is that TAF10 could serve as an interface of interaction with a LPM specific transcription factor as it has been described recently for GATA1 during erythropoiesis (Papadopoulos et al, 2015).…”

“…TAF10 does not exhibit any enzymatic activity but serves as an interface allowing interaction with other TAFs (Bieniossek et al, 2013;Trowitzsch et al, 2015) or some transcriptional factors such as human estrogen receptor a (Jacq et al, 1994) or mouse GATA1 (Papadopoulos et al, 2015). Only 50% of the TFIID complexes contain TAF10 in HeLa cells (Jacq et al, 1994).…”

Role of Anillin in Tumour: From a Prognostic Biomarker to a Novel Target

“…TAF10: Gene ontology annotations associated with the TATA-box-binding protein associated factor 10 (TAF10) are the DNA-binding transcription factor activity and the transcription coactivator activity. TAF10 is involved in the process of Drosophila erythropoiesis via the GATA1 transcription factor [84], and it appears to play a dispensable role in the somitogenesis process and the Drosophila morphogenesis process in mice [85,86]. TAF10 inactivation in liver tissue was observed to dissociate TFIID complexes individually, but genes affected by TAF10 inactivation were less than 5% of the active genes [87].…”