Despite the conventional distinction between them, promoters and enhancers share many features in mammals, including divergent transcription and similar modes of transcription factor binding. Here, we examine the architecture of transcription initiation through comprehensive mapping of transcription start sites (TSSs) in human lymphoblastoid B-cell (GM12878) and chronic myelogenous leukemic (K562) tier 1, ENCODE cell lines. Using a nuclear run-on protocol called GRO-cap, which captures TSSs for both stable and unstable transcripts, we conduct detailed comparisons of thousands of promoters and enhancers in human cells. These analyses reveal a common architecture of initiation, including tightly spaced (110 bp) divergent initiation, similar frequencies of core-promoter sequence elements, highly positioned flanking nucleosomes, and two modes of transcription factor binding. Post-initiation transcript stability provides a more fundamental distinction between promoters and enhancers than patterns of histone modifications, transcription factors or co-activators. These results support a unified model of transcription initiation at promoters and enhancers.

Besides their value for biomedicine, individual genome sequences are a rich source of information about human evolution. Here we describe an effort to estimate key evolutionary parameters from sequences for six individuals from diverse human populations. We use a Bayesian, coalescent-based approach to extract information about ancestral population sizes, divergence times, and migration rates from inferred genealogies at many neutrally evolving loci from across the genome. We introduce new methods for accommodating gene flow between populations and integrating over possible phasings of diploid genotypes. We also describe a custom pipeline for genotype inference to mitigate biases from heterogeneous sequencing technologies and coverage levels. Our analysis indicates that the San of Southern Africa diverged from other human populations 108–157 thousand years ago (kya), that Eurasians diverged from an ancestral African population 38–64 kya, and that the effective population size of the ancestors of all modern humans was ~9,000.