Chromosomal elements regulate gene activity and chromatin structure of the human serpin gene cluster at 14q32.1.
The human serine protease inhibitor (serpin) gene cluster at 14q32.1 contains a number of genes that are specifically expressed in hepatic cells. Cell-specific enhancers have been identified in several of these genes, but elements involved in locus-wide gene and chromatin control have yet to be defined. To identify regulatory elements in this region, we prepared a series of mutant chromosomal alleles by homologous recombination and transferred the specifically modified human chromosomes to hepatic cells for functional tests. We report that deletion of an 8-kb DNA segment upstream of the human alpha1-antitrypsin gene yields a mutant serpin allele that fails to be activated in hepatic cells. Within this region, a 2.3-kb DNA segment between kb -8.1 and -5.8 contains a previously unrecognized control region that is required not only for serpin gene activation but also for chromatin remodeling of the entire locus.
Marsden
Mark D
MD
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109, USA.
Fournier
R E K
RE
D000483:Alleles; D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D002875:Chromosomes / Q000378:metabolism; D002883:Chromosomes, Human, Pair 14; D004247:DNA / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D007621:Karyotyping; D008099:Liver / Q000166:cytology; D051379:Mice; D008957:Models, Genetic; D005810:Multigene Family; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D011401:Promoter Regions, Genetic; D051381:Rats; D011995:Recombination, Genetic; D015843:Serpins / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism
D002843:Chromatin; D015843:Serpins; D000515:alpha 1-Antitrypsin; D004247:DNA