HPR1 ENCODES A GLOBAL POSITIVE REGULATOR OF TRANSCRIPTION IN SACCHAROMYCES-CEREVISIAE

The Hpr1 protein has an unknown function, although it contains a regio n of homology to DNA topoisomerase I, We have found that hpr1 null mut ants are defective in the transcription of many physiologically unrela ted genes, including GAL1, HO, ADH1, and SUC2, by using a combination of Northern (RNA) blot analysis, primer extension, and upstream activa tion sequence-lacZ fusions, Many of the genes positively regulated by HPR1 also require SWI1, SWI2-SNF2, SWI3, SNF5, and SNF6. The transcrip tional defect at HO and the CCB::lacZ upstream activation sequence in hpr1 mutants is partially suppressed by a deletion of SIN1, which enco des an HMG1p-like protein, Elevated gene dosage of either histones H3 and H4 or H2A and H2B results in a severe growth defect in combination with an hpr1 null mutation. However, increased gene dosage of all fou r histones simultaneously restores near-normal growth in hpr1 mutants, Altered in vivo Dam methylase sensitivity is observed at two HPR1-dep endent promoters (GAL1 and SUC2), Most of the Hpr1 protein present in the cell is in a large complex (10(6) Da) that is distinct from the SW I-SNF protein complex, We propose that HPR1 affects transcription and recombination by altering chromatin structure.