Identification and characterization of nuclear matrix-attachment regions in the human serpin gene cluster at 14q32.1

Matrix-attachment regions (MARs) are DNA elements that are defined by their abilities to bind to isolated nuclear matrices in vitro. The DNA sequences of different matrix-binding elements vary widely, The locations of some MA Rs at the ends of chromatin loops suggest that they may represent boundarie s of individual chromatin domains. As such, MARs may play important roles i n regulating transcription and chromatin structure. As a first step towards assessing the roles of MARs in these processes,we assayed DNA sequences fr om the human serine protease inhibitor (serpin) gene cluster at 14q32.1 for matrix-binding activity in vitro, This similar to 150 kb region contains t he cell-specific genes encoding alpha 1-antitrypsin (alpha 1AT) and cortico steroid-binding globulin (CBG), as well as an antitrypsin-related sequence termed AIR. A DNase I-hypersensitive site (DHS) map of the locus has recent ly been described. We report here that the alpha 1AT-ATR-CBG region contain s five distinct MARs, There is a strong matrix-binding element similar to 1 6 kb upstream of alpha 1AT; three MARs are between ATR and CBG and one MAR is within the CBG gene itself. These MARs were matrix-associated in all cel l types examined. DNA sequencing indicated that the serpin MARs contained p redominantly repetitive DNA, although the types of DNA repeats differed amo ng the MARs.