Dynamic associations of transcription factors with the rat liver nuclear matrix are functionally related to differential alpha-2-macroglobulin gene expression

Abstract

Participation of the nuclear matrix in regulation of alpha-2-macroglobulin (α2M) gene transcription during rat liver development and the acute-phase (AP) response are examined. DNA affinity chromatography of fetal and adult liver internal nuclear matrix proteins under basal and AP conditions with the α2M gene promoter (-852/+12) and immunoblot analysis revealed diverse patterns of association of transcription factors with the nuclear matrix. HNF-6, C/EBPα, and STAT5b were involved in basal and C/EBPβ, STAT1, and STAT3 in AP-stimulated α2M expression. These findings support the assumption that transcription factor-nuclear matrix interactions serve to channel gene regulatory proteins to DNA sequences.Cilj rada je ispitivanje učešća jedarnog matriksa u regulaciji transkripcije gena za alfa-2-makroglobulin tokom razvića jetre pacova i akutno faznog odgovora (AFO). Nakon DNK afinitetne hromatografije proteina unutrašnje mreže jedarnog matriksa fetalne i adultne jetre, u bazalnim i AFO uslovima, sa promotorskim elementom gena za α2M (-852/+12) i imunoblot analize, identifikovane su dinamičke asocijacije transkripcionih faktora uključenih u regulaciju ekspresije gena za α2M sa jedarnim matriksom. HNF-6, C/EBPα, STAT5b su uključeni u regulaciju bazalne ekspresije gena za α2M, dok C/EBPβ, STAT1, STAT3 posreduju u regulaciji ekspresije ovog gena tokom AFO. Opisane interakcije doprinose razumevanju predloženih mehanizama kojima se transkripcioni faktori usmeravaju ka ciljnim regulatornim elementima DNK.Projekat ministarstva br. 143002