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Chunk #5 — Distinct PU.1 binding programs in macrophages and B cells

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Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities.
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We initially performed chromatin immunoprecipitation-coupled deep sequencing (ChIP-Seq) (Barski et al., 2007) to define the PU.1 cistromes in mouse peritoneal macrophages and splenic B cells. These analyses identified 45631 and 32575 PU.1-bound genomic sites (FDR < 0.1%) in macrophages and B cells, respectively (Table S1), which included known PU.1 target sites (Figure S1A). Of these sites, 17130 were independently identified as bound by PU.1 in both cell types (Figure 1B and 1C, and Figure S1B). PU.1 was enriched at transcription start sites (TSS) relative to their genomic frequency but the majority of binding occurred at inter- and intragenic sites (Figure S1C).