Kinetic profiles of p300 occupancy in vivo predict common features of promoter structure and coactivator recruitment.
Understanding the language encrypted in the gene regulatory regions of the human genome is a challenging goal for the genomic era. Although customary extrapolations from steady-state mRNA levels have been effective, deciphering these regulatory codes will require additional empirical data sets that more closely reflect the dynamic progression of molecular events responsible for inducible transcription. We describe an approach using chromatin immunoprecipitation to profile the kinetic occupancy of the transcriptional coactivator and histone acetyltransferase p300 at numerous mitogen-induced genes in activated T cells. Comparison of these profiles reveals a class of promoters that share common patterns of inducible expression, p300 recruitment, dependence on selective p300 domains, and sensitivity to histone deacetylase inhibitors. Remarkably, this class also shares an evolutionarily conserved promoter composition and structure that accurately predicts additional human genes with similar functional attributes. This "reverse genomic" approach will have broad application for the genome-wide classification of promoter structure and function.
Smith
James L
JL
Laboratory of Receptor Biology and Gene Expression and Microarray Facility, Advanced Technology Center, National Cancer Institute, Bethesda, MD 20892, USA.
Freebern
Wendy J
WJ
Collins
Irene
I
De Siervi
Adriana
A
Montano
Idalia
I
Haggerty
Cynthia M
CM
McNutt
Markey C
MC
Butscher
Wayne G
WG
Dzekunova
Inna
I
Petersen
David W
DW
Kawasaki
Ernest
E
Merchant
Juanita L
JL
Gardner
Kevin
K
D000123:Acetyltransferases / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence; D005786:Gene Expression Regulation / Q000187:drug effects; D051548:Histone Acetyltransferases; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D008213:Lymphocyte Activation; D008934:Mitogens / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics* / Q000502:physiology; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport; D012045:Regulatory Sequences, Nucleic Acid; D013601:T-Lymphocytes / Q000378:metabolism; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D008934:Mitogens; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor