PROPERTIES OF NUCLEAR MATRIX PROTEINS THAT BIND THE 5'-FLANKING REGION OF THE HAPTOGLOBIN GENE ARE CHANGED DURING THE ACUTE-PHASE RESPONSE

It was previously shown that during the acute-phase response-induced e levated transcription of the rat haptoglobin gene, protein p55 and the lamins mediate the increased binding of restriction fragment II (-541 /-146) via a 38 bp adenine tract lying 147 bp upstream from the haptog lobin gene cis element (-165/-56), to scaffold type II-like nuclear ma trices. Here we show that the fragment II binding pattern to greater t han or equal to 40 kDa proteins of nuclear matrices analogous to type I scaffolds is more complex. Fragment II bound conspicuously to a 40 a nd less so to p55, a 60 kDa protein and the lamins of control matrices . During increased gene transcription, it bound prominently to p55, th e lamins, and less so to 45 and 52 kDa proteins. This was accompanied by the tenacious binding of the DNA to isolated nuclear matrices in vi tro and post-translational modifications of certain matrix proteins. T he lamins and p55 demonstrated a greater N-acetylglucosamine/sialic ac id content and p55 an increased in vitro phosphorylation by a nuclear matrix-associated cyclic-nucleotide-independent kinase, The acute-phas e response also caused an increased partitioning of p55 with the nucle ar matrix. It was concluded that, as a result of a molecular remodelli ng of the nuclear matrix at the point of contact with chromatin, the n ature of its association with region II DNA changed during elevated ha ptoglobin gene expression. (C) 1996 Academic Press Limited