TY - JOUR
T1 - Chromatin states shaped by an epigenetic code confer regenerative potential to the mouse liver
AU - Zhang, Chi
AU - Macchi, Filippo
AU - Magnani, Elena
AU - Sadler, Kirsten C.
N1 - Funding Information:
We are grateful for input from the NYUAD Center for Genomics and Systems Biology, especially S. Wang for initial study and data generation, N. Drou for sequencing data processing insight, Xiyuan Zhang for insights on PRC2, and scRNAseqq analysis. B. Madakashira for preparing ATACseq libraries, S. Ranjan and B. Madakashira for the expert animal maintenance and members of the Sadler lab for critical discussion of the manuscript. This study was funded by the NYUAD Faculty Research Fund and the National Institute of Diabetes, Digestive and Kidney Diseases (2R01DK080789) to K.C.S.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - We hypothesized that the highly controlled pattern of gene expression that is essential for liver regeneration is encoded by an epigenetic code set in quiescent hepatocytes. Here we report that epigenetic and transcriptomic profiling of quiescent and regenerating mouse livers define chromatin states that dictate gene expression and transposon repression. We integrate ATACseq and DNA methylation profiling with ChIPseq for the histone marks H3K4me3, H3K27me3 and H3K9me3 and the histone variant H2AZ to identify 6 chromatin states with distinct functional characteristics. We show that genes involved in proliferation reside in active states, but are marked with H3K27me3 and silenced in quiescent livers. We find that during regeneration, H3K27me3 is depleted from their promoters, facilitating their dynamic expression. These findings demonstrate that hepatic chromatin states in quiescent livers predict gene expression and that pro-regenerative genes are maintained in active chromatin states, but are restrained by H3K27me3, permitting a rapid and synchronized response during regeneration.
AB - We hypothesized that the highly controlled pattern of gene expression that is essential for liver regeneration is encoded by an epigenetic code set in quiescent hepatocytes. Here we report that epigenetic and transcriptomic profiling of quiescent and regenerating mouse livers define chromatin states that dictate gene expression and transposon repression. We integrate ATACseq and DNA methylation profiling with ChIPseq for the histone marks H3K4me3, H3K27me3 and H3K9me3 and the histone variant H2AZ to identify 6 chromatin states with distinct functional characteristics. We show that genes involved in proliferation reside in active states, but are marked with H3K27me3 and silenced in quiescent livers. We find that during regeneration, H3K27me3 is depleted from their promoters, facilitating their dynamic expression. These findings demonstrate that hepatic chromatin states in quiescent livers predict gene expression and that pro-regenerative genes are maintained in active chromatin states, but are restrained by H3K27me3, permitting a rapid and synchronized response during regeneration.
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U2 - 10.1038/s41467-021-24466-1
DO - 10.1038/s41467-021-24466-1
M3 - Article
C2 - 34226551
AN - SCOPUS:85110894368
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4110
ER -