Selective Anchoring of TFIID to Nucleosomes by Trimethylation of Histone H3 Lysine 4

Abstract

Trimethylation of histone H3 at lysine 4 (H3K4me3) is regarded as a hallmark of active human promoters, but it remains unclear how this posttranslational modification links to transcriptional activation. Using a stable isotope labeling by amino acids in cell culture (SILAC)-based proteomic screening we show that the basal transcription factor TFIID directly binds to the H3K4me3 mark via the plant homeodomain (PHD) finger of TAF3. Selective loss of H3K4me3 reduces transcription from and TFIID binding to a subset of promoters in vivo. Equilibrium binding assays and competition experiments show that the TAF3 PHD finger is highly selective for H3K4me3. In transient assays, TAF3 can act as a transcriptional coactivator in a PHD finger-dependent manner. Interestingly, asymmetric dimethylation of H3R2 selectively inhibits TFIID binding to H3K4me3, whereas acetylation of H3K9 and H3K14 potentiates TFIID interaction. Our experiments reveal crosstalk between histone modifications and the transcription factor TFIID. This has important implications for regulation of RNA polymerase II-mediated transcription in higher eukaryotes.

A dual role of linker histone H1.4 Lys 34 acetylation in transcriptional activation

“…S6C). Note that only a fraction of TAF1 colocalizes with H1.4K34ac, consistent with the fact that this protein has been also shown to bind to acetylated core histones (Jacobson et al 2000;Agalioti et al 2002), and another TFIID subunit interacts with H3K4me3 (Vermeulen et al 2007). Thus, the above data suggest that H1.4K34ac can help recruit a transcriptional activator to promoters.…”

Non-canonical TAF complexes regulate active promoters in human embryonic stem cells

“…In this regard, TAF2 and TAF6 have been shown to interact with promoter sequence elements (reviewed in Maston et al, 2006), which may contribute to differential promoter recognition by the TBP/TAF 2,6,7,11 complex. In addition, TAF3 contains a PHD finger domain that can bind to the H3K4me3 chromatin mark (Vermeulen et al, 2007), which is enriched at class I promoters (Figure 6E). …”

Divergent transcription: A new feature of active promoters

“…3 There is also a reduction in upstream RNAPII and H3K4me3 for genes that show no upstream TSSaRNAs (Seila AC, unpublished data). These observations point to a positive feedback loop between the transcription machinery and histone modifications; whereby a pioneering round of initiation and early elongation can lead to modification of histones in the adjacent nucleosomes that will enhance future rounds of intitiation [42][43][44] (Fig. 2).…”