Stochastic expression and epigenetic memory at the yeast HO promoter

Qian Zhang, Youngdae Yoon, Yaxin Yu, Emily J. Parnell, Juan Antonio Raygoza Garay, Michael M. Mwangi, Frederick R. Cross, David J. Stillman, Lu Bai

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Eukaryotic gene regulation usually involves sequence-specific transcription factors and sequence-nonspecific cofactors. A large effort has been made to understand how these factors affect the average gene expression level among a population. However, little is known about how they regulate gene expression in individual cells. In this work, we address this question by mutating multiple factors in the regulatory pathway of the yeast HO promoter (HOpr) and probing the corresponding promoter activity in single cells using time-lapse fluorescence microscopy. We show that the HOpr fires in an "on/off" fashion in WT cells as well as in different genetic backgrounds. Many chromatin-related cofactors that affect the average level of HO expression do not actually affect the firing amplitude of the HOpr; instead, they affect the firing frequency among individual cell cycles. With certain mutations, the bimodal expression exhibits short-term epigenetic memory across the mitotic boundary. This memory is propagated in "cis" and reflects enhanced activator binding after a previous "on" cycle. We present evidence that the memory results from slow turnover of the histone acetylation marks.

Original languageEnglish (US)
Pages (from-to)14012-14017
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number34
DOIs
StatePublished - Aug 28 2013

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Epigenomics
Yeasts
Histone Code
Gene Expression
Acetylation
Short-Term Memory
Fluorescence Microscopy
Chromatin
Cell Cycle
Transcription Factors
Mutation
Population
Genes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Zhang, Qian ; Yoon, Youngdae ; Yu, Yaxin ; Parnell, Emily J. ; Garay, Juan Antonio Raygoza ; Mwangi, Michael M. ; Cross, Frederick R. ; Stillman, David J. ; Bai, Lu. / Stochastic expression and epigenetic memory at the yeast HO promoter. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 34. pp. 14012-14017.
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Zhang, Q, Yoon, Y, Yu, Y, Parnell, EJ, Garay, JAR, Mwangi, MM, Cross, FR, Stillman, DJ & Bai, L 2013, 'Stochastic expression and epigenetic memory at the yeast HO promoter', Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 34, pp. 14012-14017. https://doi.org/10.1073/pnas.1306113110

Stochastic expression and epigenetic memory at the yeast HO promoter. / Zhang, Qian; Yoon, Youngdae; Yu, Yaxin; Parnell, Emily J.; Garay, Juan Antonio Raygoza; Mwangi, Michael M.; Cross, Frederick R.; Stillman, David J.; Bai, Lu.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 34, 28.08.2013, p. 14012-14017.

Research output: Contribution to journalArticle

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