PMID- 1710768 OWN - NLM STAT- MEDLINE DCOM- 19910717 LR - 20210526 IS - 0270-7306 (Print) IS - 1098-5549 (Electronic) IS - 0270-7306 (Linking) VI - 11 IP - 7 DP - 1991 Jul TI - Identification of cis sequences controlling efficient position-independent tissue-specific expression of human major histocompatibility complex class I genes in transgenic mice. PG - 3564-72 AB - We previously reported that genomic major histocompatibility complex class I human leukocyte antigen (HLA)-B7 gene constructs with as little as 0.66 kb of 5'- and 2.0 kb of 3'-flanking DNA were expressed efficiently and appropriately in transgenic mice. To identify and characterize the relevant cis-acting regulatory elements in more detail, we have generated and analyzed a series of transgenic mice carrying native HLA-B7 genes with further 5' truncations or intronic deletions and hybrid constructs linking the 5'-flanking region of B7 to a reporter gene. We were unable to detect a specific requirement for sequence information within introns 2 to 7 for either appropriate constitutive or inducible class I expression in adult animals. The results revealed the presence of cis-acting regulatory sequences between -0.075 kb and -0.66 kb involved in driving efficient copy number-dependent constitutive and gamma interferon-enhanced tissue-specific expression. The region from -0.11 to -0.66 kb is also sufficient to prevent integration site-specific "position effects," because in its absence HLA-B7 expression is frequently detected at significant levels at inappropriate sites. Conserved sequence elements homologous to the H-2 class I regulatory element, or enhancer A, and the interferon response sequence are located between about -151 and -228 bp of the B7 gene. Our results also indicate the existence of sequences downstream of -0.11 kb which can influence the pattern of tissue-specific expression of the HLA-B7 gene and the ability of this gene to respond to gamma interferon. FAU - Chamberlain, J W AU - Chamberlain JW AD - Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada. FAU - Vasavada, H A AU - Vasavada HA FAU - Ganguly, S AU - Ganguly S FAU - Weissman, S M AU - Weissman SM LA - eng GR - CA42556/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (HLA-B7 Antigen) RN - 0 (Recombinant Proteins) RN - 63231-63-0 (RNA) RN - 82115-62-6 (Interferon-gamma) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - DNA/genetics/isolation & purification MH - Gene Expression MH - *Gene Expression Regulation/drug effects MH - *Genes, MHC Class I MH - *Genes, Regulator MH - HLA-B7 Antigen/*genetics MH - Humans MH - Interferon-gamma/pharmacology MH - Mice MH - Mice, Transgenic MH - Nucleic Acid Hybridization MH - RNA/genetics/isolation & purification MH - Recombinant Proteins MH - Transcription, Genetic/drug effects PMC - PMC361100 EDAT- 1991/07/01 00:00 MHDA- 1991/07/01 00:01 PMCR- 1991/07/01 CRDT- 1991/07/01 00:00 PHST- 1991/07/01 00:00 [pubmed] PHST- 1991/07/01 00:01 [medline] PHST- 1991/07/01 00:00 [entrez] PHST- 1991/07/01 00:00 [pmc-release] AID - 10.1128/mcb.11.7.3564-3572.1991 [doi] PST - ppublish SO - Mol Cell Biol. 1991 Jul;11(7):3564-72. doi: 10.1128/mcb.11.7.3564-3572.1991.