The Replication-independent H3-H4 chaperones HIR, Asf1 and Rtt106 Co-operate to Maintain Promoter Fidelity
Silva, Andrea C.
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RNA polymerase II initiates from low-complexity sequences so cells must reliably distinguish 'real' from 'cryptic' promoters and maintain fidelity to the former. Further this must be performed under a range of conditions, including those found within inactive and highly transcribed regions. We hypothesized that factors that prevent cryptic transcription maintain the cells' faithfulness to canonical over cryptic promoters. Here we used genome-scale screening to identify those factors that regulate the use of a specific cryptic promoter, and how this is influenced by the degree of transcription over the element. We show that promoter fidelity is most reliant on histone gene transactivators (Spt10, Spt21) and H3-H4 chaperones (Asf1, HIR complex) from the replication-independent deposition (RID) pathway. Mutations of Rtt106 that abrogate its interactions with H3-H4 or dsDNA permit extensive cryptic transcription comparable to RID factor deletions. We propose that nucleosome shielding is the primary means to maintain promoter fidelity, and histone replacement is most efficiently mediated in yeast cells by a [HIR : Asf1 : H3-H4 : Rtt106] pathway.
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