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 elevated 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 haptoglobin gene cis element (-165/-56), to scaffold type II-like nuclear matrices. Here we show that the fragment II binding pattern to > or = 40 kDa proteins of nuclear matrices analogous to type I scaffolds is more complex. Fragment II bound conspicuously to a 40 and less so to p55, a 60 kDa protein and the lamins of control matrices. During increased gene transcription, it bound prominently to p55, the 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 vitro and post-translational modifications of certain matrix proteins. The lamins and p55 demonstrated a greater N-acetylglucosamine/sialic acid content and p55 an increased in vitro phosphorylation by a nuclear matrix-associated cyclic-nucleotide-independent kinase. The acute-phase response also caused an increased partitioning of p55 with the nuclear matrix. It was concluded that, as a result of a molecular remodelling of the nuclear matrix at the point of contact with chromatin, the nature of its association with region II DNA changed during elevated haptoglobin gene expression.