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Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities.

Molecular cell | May 28, 2010

Genome-scale studies have revealed extensive, cell type-specific colocalization of transcription factors, but the mechanisms underlying this phenomenon remain poorly understood. Here, we demonstrate in macrophages and B cells that collaborative interactions of the common factor PU.1 with small sets of macrophage- or B cell lineage-determining transcription factors establish cell-specific binding sites that are associated with the majority of promoter-distal H3K4me1-marked genomic regions. PU.1 binding initiates nucleosome remodeling, followed by H3K4 monomethylation at large numbers of genomic regions associated with both broadly and specifically expressed genes. These locations serve as beacons for additional factors, exemplified by liver X receptors, which drive both cell-specific gene expression and signal-dependent responses. Together with analyses of transcription factor binding and H3K4me1 patterns in other cell types, these studies suggest that simple combinations of lineage-determining transcription factors can specify the genomic sites ultimately responsible for both cell identity and cell type-specific responses to diverse signaling inputs.

Pubmed ID: 20513432 RIS Download

Mesh terms: Animals | B-Lymphocytes | Binding Sites | Cell Lineage | Macrophages | Male | Mice | Mice, Inbred C57BL | Oligonucleotide Array Sequence Analysis | Proto-Oncogene Proteins | Regulatory Elements, Transcriptional | Trans-Activators | Transcription Factors

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Associated grants

  • Agency: NIGMS NIH HHS, Id: P50 GM081892-01A1
  • Agency: NIGMS NIH HHS, Id: P50 GM081892
  • Agency: NIDDK NIH HHS, Id: P30 DK063491-039003
  • Agency: NCI NIH HHS, Id: R01 CA052599-19
  • Agency: NIDDK NIH HHS, Id: U19 DK062434-080007
  • Agency: NHLBI NIH HHS, Id: HC088093
  • Agency: NHLBI NIH HHS, Id: F32 HL083752
  • Agency: NIDDK NIH HHS, Id: P30 DK063491-029003
  • Agency: NIDDK NIH HHS, Id: U19 DK062434-060007
  • Agency: NIDDK NIH HHS, Id: U19 DK062434
  • Agency: NCI NIH HHS, Id: R01 CA052599-20
  • Agency: NCI NIH HHS, Id: R01 CA052599
  • Agency: NIDDK NIH HHS, Id: R01 DK091183
  • Agency: NIDDK NIH HHS, Id: P30 DK063491-019003
  • Agency: NIDDK NIH HHS, Id: P30 DK063491
  • Agency: NCI NIH HHS, Id: R01 CA054198
  • Agency: NIDDK NIH HHS, Id: U19 DK062434-08S10007
  • Agency: NIDDK NIH HHS, Id: P30 DK063491-049003
  • Agency: NIDDK NIH HHS, Id: DK62434
  • Agency: NCI NIH HHS, Id: CA52599
  • Agency: NIDDK NIH HHS, Id: U19 DK062434-070007
  • Agency: NIDDK NIH HHS, Id: DK063491
  • Agency: NCI NIH HHS, Id: R01 CA052599-17
  • Agency: NCI NIH HHS, Id: R01 CA052599-18
  • Agency: NCI NIH HHS, Id: R01 CA078384

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A commercial organism provider selling mice, rats and other model animals. American corporation specializing in a variety of pre-clinical and clinical laboratory services for the pharmaceutical, medical device and biotechnology industries. It also supplies assorted biomedical products and research and development outsourcing services for use in the pharmaceutical industry. (Wikipedia)

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