Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylation
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Animals
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Binding Sites
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Chromatin / genetics
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Chromatin / metabolism
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DNA-Binding Proteins / metabolism*
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Female
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Gene Expression Regulation / genetics*
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Histones / metabolism*
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Human Growth Hormone / genetics*
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Humans
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Locus Control Region / physiology*
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Mice
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Mice, Transgenic
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Organ Specificity
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Pituitary Gland, Anterior / metabolism
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Pregnancy
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Promoter Regions, Genetic
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Protein Processing, Post-Translational*
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Sequence Deletion
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Transcription Factor Pit-1
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Transcription Factors / metabolism*
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Transcription, Genetic
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Transcriptional Activation
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Transgenes
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Trophoblasts / metabolism
Substances
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Chromatin
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DNA-Binding Proteins
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Histones
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POU1F1 protein, human
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Pit1 protein, mouse
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Transcription Factor Pit-1
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Transcription Factors
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Human Growth Hormone