A high-resolution map of active promoters in the human genome was developed using chromatin immunoprecipitation coupled DNA microarray analysis (ChIP-on-chip). This study identified 10,571 active promoters corresponding to 6,763 known genes and at least 1,199 un-annotated transcriptional units. The map revealed extensive usage of multiple promoters by human genes and widespread clustering of active promoters in the genome. Four general classes of promoters were identified, defining the transcriptome of the cell. These results provide a global view of the functional relationship among the transcriptional machinery, chromatin structure, and gene expression in human cells. The PIC consists of RNA Polymerase II (RNAP), the transcription factor IID (TFIID), and other general transcription factors. The study used ChIP-on-chip to map PIC binding sites, identifying 12,150 TFIID-binding sites. These sites were matched to known transcripts, revealing 9,330 TFIID-binding sites within 500 bp of the putative transcription start sites (TSS). These were defined as promoters for the corresponding transcripts. The study also identified 1,241 putative promoters corresponding to previously un-annotated transcription units. The active promoter map in IMR90 cells allowed systematic investigation of the functional relationship between the transcription machinery and gene expression. The study examined genome-wide expression profiles and correlated the expression status of 14,437 EnsEMBL genes to promoter occupancy by the PIC. Four general classes of genes were identified, with class I and class IV genes representing over 75% of the examined genes. Class II and III genes were inconsistent with the general model of PIC formation leading to transcription, suggesting other mechanisms may be responsible for their expression. The study also examined histone modifications (AcH3 and MeH3K4) in 29 ENCODE regions, finding that these markers were associated with virtually all class I and class II genes, and the vast majority of class III genes. However, roughly 20% of class IV genes were also associated with these markers, suggesting that a significant number of genes not actively transcribed are also associated with these markers. The results provide an initial framework for analysis of the cis-regulatory logic in human cells. The high-resolution map of active promoters in IMR90 cells will enable detailed analysis of transcription factor binding sites within these regions. The promoter map described here can also serve as a reference to understand gene expression in other cell types. The study suggests that there may be additional 13% of the human genes that remain to be annotated in the genome.A high-resolution map of active promoters in the human genome was developed using chromatin immunoprecipitation coupled DNA microarray analysis (ChIP-on-chip). This study identified 10,571 active promoters corresponding to 6,763 known genes and at least 1,199 un-annotated transcriptional units. The map revealed extensive usage of multiple promoters by human genes and widespread clustering of active promoters in the genome. Four general classes of promoters were identified, defining the transcriptome of the cell. These results provide a global view of the functional relationship among the transcriptional machinery, chromatin structure, and gene expression in human cells. The PIC consists of RNA Polymerase II (RNAP), the transcription factor IID (TFIID), and other general transcription factors. The study used ChIP-on-chip to map PIC binding sites, identifying 12,150 TFIID-binding sites. These sites were matched to known transcripts, revealing 9,330 TFIID-binding sites within 500 bp of the putative transcription start sites (TSS). These were defined as promoters for the corresponding transcripts. The study also identified 1,241 putative promoters corresponding to previously un-annotated transcription units. The active promoter map in IMR90 cells allowed systematic investigation of the functional relationship between the transcription machinery and gene expression. The study examined genome-wide expression profiles and correlated the expression status of 14,437 EnsEMBL genes to promoter occupancy by the PIC. Four general classes of genes were identified, with class I and class IV genes representing over 75% of the examined genes. Class II and III genes were inconsistent with the general model of PIC formation leading to transcription, suggesting other mechanisms may be responsible for their expression. The study also examined histone modifications (AcH3 and MeH3K4) in 29 ENCODE regions, finding that these markers were associated with virtually all class I and class II genes, and the vast majority of class III genes. However, roughly 20% of class IV genes were also associated with these markers, suggesting that a significant number of genes not actively transcribed are also associated with these markers. The results provide an initial framework for analysis of the cis-regulatory logic in human cells. The high-resolution map of active promoters in IMR90 cells will enable detailed analysis of transcription factor binding sites within these regions. The promoter map described here can also serve as a reference to understand gene expression in other cell types. The study suggests that there may be additional 13% of the human genes that remain to be annotated in the genome.