SAF-B PROTEIN COUPLES TRANSCRIPTION AND PRE-MESSENGER-RNA SPLICING TOSAR MAR ELEMENTS/

Interphase chromatin is arranged into topologically separated domains comprising gene expression and replication units through genomic seque nce elements, so-called MAR or SAR regions (for matrix- or scaffold-as sociating regions). S/MAR regions are located near the boundaries of a ctively transcribed genes and were shown to influence their activity. We show that scaffold attachment factor B (SAF-B), which specifically binds to S/MAR regions, interacts with RNA polymerase II (RNA pol II) and a subset of serine-/arginine-rich RNA processing factors (SR prote ins). SAF-B localized to the nucleus in a speckled pattern that coinci ded with the distribution of the SR protein SC35. Furthermore, we show that overexpressed SAF-B induced an increase of the 10S splice produc t using an E1A reporter gene and repressed the activity of an S/MAR fl anked CAT reporter gene construct in vivo. This indicates an associati on of SAF-B with SR proteins and components of the transcription machi nery. Our results describe the coupling of a chromatin organizing S/MA R element with transcription and pre-mRNA processing components and we propose that SAFE serves as a molecular base to assemble a 'transcrip tosome complex' in the vicinity of actively transcribed genes.