Deciphering the transcriptional histone acetylation code for a human gene.
We report the results of experiments designed to test the histone code hypothesis. We found that only a small subset of lysines in histones H4 and H3 are acetylated in vivo by the GCN5 acetyltransferase during activation of the IFN-beta gene. Reconstitution of recombinant nucleosomes bearing mutations in these lysine residues revealed the cascade of gene activation via a point-by-point interpretation of the histone code through the ordered recruitment of bromodomain-containing transcription complexes. Acetylation of histone H4 K8 mediates recruitment of the SWI/SNF complex whereas acetylation of K9 and K14 in histone H3 is critical for the recruitment of TFIID. Thus, the information contained in the DNA address of the enhancer is transferred to the histone N termini by generating novel adhesive surfaces required for the recruitment of transcription complexes.
Agalioti
Theodora
T
Department of Biochemistry and Molecular Biophysics, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
Chen
Guoying
G
Thanos
Dimitris
D
D000107:Acetylation; D004265:DNA Helicases; D004742:Enhancer Elements, Genetic; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D016899:Interferon-beta / Q000235:genetics*; D009687:Nuclear Proteins / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D029082:Sendai virus / Q000502:physiology; D035362:Transcription Factor TFIID / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D016899:Interferon-beta; C084108:SMARCA4 protein, human; D004265:DNA Helicases