Systematic Analysis of the Determinants of Gene Expression Noise in Embryonic Stem Cells.

Abstract:

:Isogenic cells in a common environment show substantial cell-to-cell variation in gene expression, often referred to as "expression noise." Here, we use multiple single-cell RNA-sequencing datasets to identify features associated with high or low expression noise in mouse embryonic stem cells. These include the core promoter architecture of a gene, with CpG island promoters and a TATA box associated with low and high noise, respectively. High noise is also associated with "conflicting" chromatin states-the absence of transcription-associated histone modifications or the presence of repressive ones in active genes. Genes regulated by pluripotency factors through super-enhancers show high and correlated expression variability, consistent with fluctuations in the pluripotent state. Together, our results provide an integrated view of how core promoters, chromatin, regulation, and pluripotency fluctuations contribute to the variability of gene expression across individual stem cells.

journal_name

Cell Syst

journal_title

Cell systems

authors

Faure AJ,Schmiedel JM,Lehner B

doi

10.1016/j.cels.2017.10.003

subject

Has Abstract

pub_date

2017-11-22 00:00:00

pages

471-484.e4

issue

5

eissn

2405-4712

issn

2405-4720

pii

S2405-4712(17)30440-4

journal_volume

5

pub_type

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