Pontin functions as an essential coactivator for Oct4-dependent lincRNA expression in mouse embryonic stem cells

Kyungjin Boo; Jinhyuk Bhin; Yoon Jeon; Joomyung Kim; Hi-Jai R Shin; Jong-Eun Park; Kyeongkyu Kim; Chang Rok Kim; Hyonchol Jang; In-Hoo Kim; V Narry Kim; Daehee Hwang; Ho Lee; Sung Hee Baek

doi:10.1038/ncomms7810

Pontin functions as an essential coactivator for Oct4-dependent lincRNA expression in mouse embryonic stem cells

Nat Commun. 2015 Apr 10:6:6810. doi: 10.1038/ncomms7810.

Authors

Affiliations

¹ Creative Research Initiative Center for Chromatin Dynamics, School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea.
² Department of Chemical Engineering, POSTECH, Pohang 790-784, South Korea.
³ Research Institute, Graduate School of Cancer Science and Policy, National Cancer Center, Gyeonggi-do 410-769, South Korea.
⁴ Institute for Basic Science, School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea.
⁵ 1] Department of Chemical Engineering, POSTECH, Pohang 790-784, South Korea [2] Department of New Biology and Center for Plant Aging Research, Institute for Basic Science, DGIST, Daegu 711-873, South Korea.

Abstract

The actions of transcription factors, chromatin modifiers and noncoding RNAs are crucial for the programming of cell states. Although the importance of various epigenetic machineries for controlling pluripotency of embryonic stem (ES) cells has been previously studied, how chromatin modifiers cooperate with specific transcription factors still remains largely elusive. Here, we find that Pontin chromatin remodelling factor plays an essential role as a coactivator for Oct4 for maintenance of pluripotency in mouse ES cells. Genome-wide analyses reveal that Pontin and Oct4 share a substantial set of target genes involved in ES cell maintenance. Intriguingly, we find that the Oct4-dependent coactivator function of Pontin extends to the transcription of large intergenic noncoding RNAs (lincRNAs) and in particular linc1253, a lineage programme repressing lincRNA, is a Pontin-dependent Oct4 target lincRNA. Together, our findings demonstrate that the Oct4-Pontin module plays critical roles in the regulation of genes involved in ES cell fate determination.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Chromatin / chemistry
Chromatin / metabolism
Chromatin Assembly and Disassembly
DNA Helicases / deficiency
DNA Helicases / genetics*
Epigenesis, Genetic*
Gene Expression Profiling
Genome-Wide Association Study
Mice
Mice, Knockout
Mouse Embryonic Stem Cells / cytology
Mouse Embryonic Stem Cells / metabolism*
Octamer Transcription Factor-3 / deficiency
Octamer Transcription Factor-3 / genetics*
Patched Receptors
Pluripotent Stem Cells / cytology
Pluripotent Stem Cells / metabolism
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism
Receptors, Cell Surface / genetics
Receptors, Cell Surface / metabolism
Signal Transduction
Telomere-Binding Proteins / genetics
Telomere-Binding Proteins / metabolism
Tissue Inhibitor of Metalloproteinase-2 / genetics
Tissue Inhibitor of Metalloproteinase-2 / metabolism
Tropomyosin / genetics
Tropomyosin / metabolism

Substances

Chromatin
Octamer Transcription Factor-3
Patched Receptors
Pou5f1 protein, mouse
RNA, Long Noncoding
Receptors, Cell Surface
Rif1 protein, mouse
Telomere-Binding Proteins
Tpm1 protein, mouse
Tropomyosin
Tissue Inhibitor of Metalloproteinase-2
TIP48 protein, mouse
DNA Helicases