Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities.
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.
Heinz
Sven
S
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Benner
Christopher
C
Spann
Nathanael
N
Bertolino
Eric
E
Lin
Yin C
YC
Laslo
Peter
P
Cheng
Jason X
JX
Murre
Cornelis
C
Singh
Harinder
H
Glass
Christopher K
CK
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D001665:Binding Sites; D019070:Cell Lineage / Q000235:genetics; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1