TY - JOUR
T1 - Selective Anchoring of TFIID to Nucleosomes by Trimethylation of Histone H3 Lysine 4
AU - Vermeulen, Michiel
AU - Mulder, Klaas W.
AU - Denissov, Sergei
AU - Pijnappel, W. W.M.Pim
AU - van Schaik, Frederik M.A.
AU - Varier, Radhika A.
AU - Baltissen, Marijke P.A.
AU - Stunnenberg, Henk G.
AU - Mann, Matthias
AU - Timmers, H. Th Marc
N1 - Funding Information:
This work was supported by grants to the Timmers lab from the European Union (STREP LSHG-CT-2004-502950) and the Netherlands Proteomics Centre. Furthermore, the work in the Mann and Stunnenberg labs is supported by HEROIC, an Integrated Project funded by the European Union under the 6th Framework Programme (LSHG-CT-2005-018883). The research of M.V. is supported by a TALENT grant of the Netherlands Organization for Scientific Research (NWO) and by a fellowship of the Dutch Cancer Society (KWF/NKB).
PY - 2007/10/5
Y1 - 2007/10/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34848911602&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2007.08.016
DO - 10.1016/j.cell.2007.08.016
M3 - Article
C2 - 17884155
AN - SCOPUS:34848911602
SN - 0092-8674
VL - 131
SP - 58
EP - 69
JO - Cell
JF - Cell
IS - 1
ER -