BINDING OF MATRIX ATTACHMENT REGIONS TO LAMIN POLYMERS INVOLVES SINGLE-STRANDED REGIONS AND THE MINOR-GROOVE

Chromatin in eukaryotic nuclei is thought to be partitioned into funct ional loop domains that are generated by the binding of defined DNA se quences, named MARs (matrix attachment regions), to the nuclear matrix . We have previously identified B-type lamins as MAR-binding matrix co mponents (M. E. E. Luderus, A. de Graaf, E. Mattia, J. L. den Blaauwen , M. A. Grande, L. de Jong, and R. van Driel, Cell 70:949-959, 1992). Here we show that A-type lamins and the structurally related proteins desmin and NuMA also specifically bind MARs in vitro. We studied the i nteraction between MARs and lamin polymers in molecular detail and fou nd that the interaction is saturable, of high affinity, and evolutiona rily conserved. Competition studies revealed the existence of two diff erent types of interaction related to different structural features of MARs: one involving the minor groove of double-stranded MAR DNA and o ne involving single-stranded regions. We obtained similar results for the interaction of MARs with intact nuclear matrices from rat liver. A model in which the interaction of nuclear matrix proteins with single -stranded MAR regions serves to stabilize the transcriptionally active state of chromatin is discussed.