A defined locus control region determinant links chromatin domain acetylation with long-range gene activation.
Gene activation in higher eukaryotes is often under the control of regulatory elements quite distant from their target promoters. It is unclear how such long-range control is mediated. Here we show that a single determinant of the human growth hormone locus control region (hGH LCR) located 14.5 kb 5prime prime or minute to the hGH-N promoter has a critical, specific, and nonredundant role in facilitating promoter trans factor binding and activating hGH-N transcription. Significantly, this same determinant plays an essential role in establishing a 32 kb acetylated domain that encompasses the entire hGH LCR and the contiguous hGH-N promoter. These data support a model for long-range gene activation via LCR-mediated targeting and extensive spreading of core histone acetylation.
Ho
Yugong
Y
Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Elefant
Felice
F
Cooke
Nancy
N
Liebhaber
Stephen
S
D000107:Acetylation; D000818:Animals; D001665:Binding Sites; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D019382:Human Growth Hormone / Q000235:genetics*; D006801:Humans; D019901:Locus Control Region / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D017384:Sequence Deletion; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D019076:Transgenes; D014327:Trophoblasts / Q000378:metabolism
D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D019382:Human Growth Hormone; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; C494187:POU1F1 protein, human; C494185:Pou1f1 protein, mouse