biostudies-literatureGvozdenov ZGoogleNational Institutes of HealthNIGMS NIH HHS1786-1797.e5https://www.ebi.ac.uk/biostudies/studies/S-EPMC10247422biostudies-literatureUnknown83(11)We measure transcriptional noise in yeast by analyzing chromatin structure and transcription of an 18-kb region of DNA whose sequence was randomly generated. Nucleosomes fully occupy random-sequence DNA, but nucleosome-depleted regions (NDRs) are much less frequent, and there are fewer well-positioned nucleosomes and shorter nucleosome arrays. Steady-state levels of random-sequence RNAs are comparable to yeast mRNAs, although transcription and decay rates are higher. Transcriptional initiation from random-sequence DNA occurs at numerous sites, indicating very low intrinsic specificity of the RNA Pol II machinery. In contrast, poly(A) profiles of random-sequence RNAs are roughly comparable to those of yeast mRNAs, suggesting limited evolutionary restraints on poly(A) site choice. Random-seqMolecular cellFunctional analysis of a random-sequence chromosome reveals a high level and the molecular nature of transcriptional noise in yeast cells.PMC10247422R01 GM030186R35 GM131801F32 GM140555GM131801GM301861F32GM140555R37 GM030186Barcutean ZGvozdenov ZStruhl KfalseFunctional analysis of a random-sequence chromosome reveals a high level and the molecular nature of transcriptional noise in yeast cells.We measure transcriptional noise in yeast by analyzing chromatin structure and transcription of an 18-kb region of DNA whose sequence was randomly generated. Nucleosomes fully occupy random-sequence DNA, but nucleosome-depleted regions (NDRs) are much less frequent, and there are fewer well-positioned nucleosomes and shorter nucleosome arrays. Steady-state levels of random-sequence RNAs are comparable to yeast mRNAs, although transcription and decay rates are higher. Transcriptional initiation from random-sequence DNA occurs at numerous sites, indicating very low intrinsic specificity of the RNA Pol II machinery. In contrast, poly(A) profiles of random-sequence RNAs are roughly comparable to those of yeast mRNAs, suggesting limited evolutionary restraints on poly(A) site choice. Random-seq2023-01-01T00:00:00Z2023 Jun2026-06-02T12:02:44.885Z2025-06-27T03:05:23.391ZS-EPMC102474223713730210.1016/j.molcel.2023.04.010