transcription fidelity and yeast aging

reviewers asks for mutation in DNA as a model. This is not correct (No, this is relavent 2020Oct), because yeast aging is a single-cell event. Its chromosome DNA unlikely to be mutated.

Experimental verification

Single cell variation

Old cell variation, 

Test of some mutants ???. On transcription fidelity,

Candidate genes: 

Transcriptional noise regulators. 

Maybe histone methylation, K4 methyltransferase? Transcript inititiation? KO? Over-expression? 

K4-methy hot in human aging. Six paralogs in human, involved in leukemia. 

Only one copy gene in yeast. No clear phenotype on growth fitness and aging in yeast. ?!!!! 

*** SET1 maybe not a general transcription initiation??? Only in stress-response. 

https://www.yeastgenome.org/locus/S000001161

Aging is a stress condition. 

TODO: SET1 expression during aging in eLife Data set. and Dang’s lab RNA and protein level data. 

Gene Ontology Term: maintenance of transcriptional fidelity during DNA-templated transcription elongation

https://www.yeastgenome.org/go/GO:0001192

**** RPB9-deletion shorten RLS by 44% with p=1E-9. -> expect to increase expression noise -> aging. 

General transcription elongation factor

https://www.yeastgenome.org/locus/DST1

DST1-deletion does change average RLS. (Need to check its distribution of RLS, gene expression). 

RPB9
https://www.yeastgenome.org/locus/S000003038
RNA polymerase II subunit B12.6; contacts DNA; mutations affect transcription start site selection and fidelity of transcription 

DST1 / YGL043W Overview

https://www.yeastgenome.org/locus/S000003011

K4 methyltransferase yeast  cerevisiae is SET1