Dynamics of promoter bivalency and RNAP II pausing in mouse stem and differentiated cells.

TitleDynamics of promoter bivalency and RNAP II pausing in mouse stem and differentiated cells.
Publication TypeJournal Article
Year of Publication2018
AuthorsMantsoki, A, Devailly, G, Joshi, A
JournalBMC Dev Biol
Date Published2018 Feb 20

BACKGROUND: Mammalian embryonic stem cells display a unique epigenetic and transcriptional state to facilitate pluripotency by maintaining lineage-specification genes in a poised state. Two epigenetic and transcription processes involved in maintaining poised state are bivalent chromatin, characterized by the simultaneous presence of activating and repressive histone methylation marks, and RNA polymerase II (RNAPII) promoter proximal pausing. However, the dynamics of histone modifications and RNAPII at promoters in diverse cellular contexts remains underexplored.RESULTS: We collected genome wide data for bivalent chromatin marks H3K4me3 and H3K27me3, and RNAPII (8WG16) occupancy together with expression profiling in eight different cell types, including ESCs, in mouse. The epigenetic and transcription profiles at promoters grouped in over thirty clusters with distinct functional identities and transcription control.CONCLUSION: The clustering analysis identified distinct bivalent clusters where genes in one cluster retained bivalency across cell types while in the other were mostly cell type specific, but neither showed a high RNAPII pausing. We noted that RNAPII pausing is more associated with active genes than bivalent genes in a cell type, and was globally reduced in differentiated cell types compared to multipotent.

Alternate JournalBMC Dev. Biol.
PubMed ID29458328
PubMed Central IDPMC5819258
Grant ListBBSRC, BB/J004235/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
PCOFUND-GA-2012-600181 / / H2020 Marie Skłodowska-Curie Actions /