title: In vivo expression of MHC class I genes depends on the presence of a downstream barrier element.
abstract: Regulation of MHC class I gene expression is critical to achieve proper immune surveillance. In this work, we identify elements downstream of the MHC class I promoter that are necessary for appropriate in vivo regulation: a novel barrier element that protects the MHC class I gene from silencing and elements within the first two introns that contribute to tissue specific transcription. The barrier element is located in intergenic sequences 3' to the polyA addition site. It is necessary for stable expression in vivo, but has no effect in transient transfection assays. Accordingly, in both transgenic mice and stably transfected cell lines, truncation of the barrier resulted in transcriptional gene silencing, increased nucleosomal density and decreased histone H3K9/K14 acetylation and H3K4 di-methylation across the gene. Significantly, distinct sequences within the barrier element govern anti-silencing and chromatin modifications. Thus, this novel barrier element functions to maintain transcriptionally permissive chromatin organization and prevent transcriptional silencing of the MHC class I gene, ensuring it is poised to respond to immune signaling.
authors.affiliation: Experimental Immunology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Helit
authors.initials: H
authors.lastname: Cohen
authors.forename: Palak
authors.initials: P
authors.lastname: Parekh
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Sercan
authors.forename: Aparna
authors.initials: A
authors.lastname: Kotekar
authors.forename: Jocelyn D
authors.initials: JD
authors.lastname: Weissman
authors.forename: Dinah S
authors.initials: DS
authors.lastname: Singer
mesh_terms: D000107:Acetylation; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D047369:Chromatin Immunoprecipitation; D018899:CpG Islands; D017931:DNA Primers; D015870:Gene Expression; D020868:Gene Silencing; D005805:Genes, MHC Class I; D007438:Introns; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers
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