Alternative splicing links histone modifications to stem cell fate decision

Genome Biology
Yungang XuXiaobo Zhou

Abstract

Understanding the embryonic stem cell (ESC) fate decision between self-renewal and proper differentiation is important for developmental biology and regenerative medicine. Attention has focused on mechanisms involving histone modifications, alternative pre-messenger RNA splicing, and cell-cycle progression. However, their intricate interrelations and joint contributions to ESC fate decision remain unclear. We analyze the transcriptomes and epigenomes of human ESC and five types of differentiated cells. We identify thousands of alternatively spliced exons and reveal their development and lineage-dependent characterizations. Several histone modifications show dynamic changes in alternatively spliced exons and three are strongly associated with 52.8% of alternative splicing events upon hESC differentiation. The histone modification-associated alternatively spliced genes predominantly function in G2/M phases and ATM/ATR-mediated DNA damage response pathway for cell differentiation, whereas other alternatively spliced genes are enriched in the G1 phase and pathways for self-renewal. These results imply a potential epigenetic mechanism by which some histone modifications contribute to ESC fate decision through the regulation of alter...Continue Reading

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Jul 6, 2019·PloS One·Adam P TellierJesse Mager
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Aug 28, 2021·Cancers·Anna WojtuszkiewiczTorsten Haferlach

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Datasets Mentioned

BETA
GSE16256
GSE18927

Methods Mentioned

BETA
immunoprecipitation
acetylation
RNA-seq
histone acetylation
ChIP-seq
PCR
electrophoresis
RIP

Software Mentioned

Weka
MISO
StemChecker
AmiGO
rMATS
R package
LiftOver
R
ImageJ
Cufflinks

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