The 3' untranslated region of the human poly(ADP-ribose) polymerase gene is a nuclear matrix anchoring site

The nuclear matrix displays the most dramatic changes among all cellular structures during carcinogenesis. Matrix attachment regions (MARs) organize chromatin into domains, harbor origins of replication and display a notable transcriptional enhancer activity. To understand the nature of MARs and their involvement in gene expression, replication, and carcinogenesis, we have cloned the MAR DNA fragments, of a size of 0.1-5.0 kb, isolated from human cells in culture. Over 150 clones have been sequenced. One MAR clone was identified as a stretch of 393 bp from the 3' untranslated region (3' UTR) of the human poly(ADP-ribose) polymerase (PARR) gene (100% homology). The 393 bp MAR fragment contains several repeats of TTGTTTTGT and related sequences (the TG boxes) and motifs with similarity to the binding site of the general yeast transcription factor GFI and to the ARS origins of replication in yeast. In addition, the 3' UTR of the PARP gene harbors MAR-type sequences found in other genes, kinked and curved DNA, two imperfect inverted repeats, and short alternating GA- and CT-rich motifs. The presence of TG-, GA-, and CT-rich motifs and of potential cruciforms is proposed to identify a novel type of MAR sequence. This report suggests that MAR sequences may reside in the 3' untranslated region of other genes and has important implications for a potential role of the nuclear matrix in transcription termination.