Differential transcription factor occupancy but evolutionarily conserved chromatin features at the human and mouse M-CSF (CSF-1) receptor loci.
The c-FMS gene encodes the macrophage colony-stimulating factor receptor (M-CSFR or CSF1-R), which is a tyrosine kinase growth factor receptor essential for macrophage development. We have previously characterized the chromatin features of the mouse gene; however, very little is known about chromatin structure and function of the human c-FMS locus. Here we present a side-by-side comparison of the chromatin structure, histone modification, transcription factor occupancy and cofactor recruitment of the human and the mouse c-FMS loci. We show that, similar to the mouse gene, the human c-FMS gene possesses a promoter and an intronic enhancer element (c-fms intronic regulatory element or FIRE). Both elements are evolutionarily conserved and specifically active in macrophages. However, we demonstrate by in vivo footprinting that both murine and human c-FMS cis-regulatory elements are recognised by an overlapping, but non-identical, set of transcription factors. Despite these differences, chromatin immunoprecipitation experiments show highly similar patterns of histone H3 modification and a similar distribution of chromatin modifying and remodelling activities at individual cis-regulatory elements and across the c-FMS locus. Our experiments support the hypothesis that the same regulatory principles operate at both genes via conserved cores of transcription factor binding sites.
Follows
George A
GA
Molecular Medicine Unit, University of Leeds, St James's University Hospital, Leeds LS9 7TF, UK.
Tagoh
Hiromi
H
Lefevre
Pascal
P
Morgan
Gareth J
GJ
Bonifer
Constanze
C
D016475:3T3 Cells; D000107:Acetylation; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics; D019143:Evolution, Molecular; D018922:HL-60 Cells; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D007438:Introns / Q000235:genetics; D008239:Lysine / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D035181:TATA-Box Binding Protein / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D002843:Chromatin; D006657:Histones; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; D016186:Receptor, Macrophage Colony-Stimulating Factor; D008239:Lysine