Similar Datasets
Project description:The inability to derive fully functional cell types, such as hepatocytes, from stem cells may emanate from the lack of knowledge about mechanisms that underlie postnatal cell maturation. We characterized hepatic maturation during the postnatal day 14 (P14) to 2-month-old (M2) transition and found more than 3000 genes differentially expressed. Nearly half of such maturation genes have H3K27me3 at their promoters or gene bodies at P14 or M2. Genetic ablation of both PRC2 histone methyltransferases in perinatal livers causes hepatocytes to prematurely differentiate, expressing genes at P14 that would normally be induced later, by M2. Using srHC-seq, a new method to map sonication-resistant heterochromatin, we found that the H3K27me3+ prematurely upregulated genes have euchromatic promoters at P14. We also observed derepression of many non-hepatic lineage genes with euchromatic promoter H3K27me3-marking. Thus, Polycomb repression is used to restrain expression of late liver maturation genes and lineage inappropriate genes at euchromatic promoters.
2019-03-01 | GSE125526 | GEO
Project description:The inability to derive fully functional cell types, such as hepatocytes, from stem cells may emanate from the lack of knowledge about mechanisms that underlie postnatal cell maturation. We characterized hepatic maturation during the postnatal day 14 (P14) to 2-month-old (M2) transition and found more than 3000 genes differentially expressed. Nearly half of such maturation genes have H3K27me3 at their promoters or gene bodies at P14 or M2. Genetic ablation of both PRC2 histone methyltransferases in perinatal livers causes hepatocytes to prematurely differentiate, expressing genes at P14 that would normally be induced later, by M2. Using srHC-seq, a new method to map sonication-resistant heterochromatin, we found that the H3K27me3+ prematurely upregulated genes have euchromatic promoters at P14. We also observed derepression of many non-hepatic lineage genes with euchromatic promoter H3K27me3-marking. Thus, Polycomb repression is used to restrain expression of late liver maturation genes and lineage inappropriate genes at euchromatic promoters.
2019-03-01 | GSE119218 | GEO
Project description:The inability to derive fully functional cell types, such as hepatocytes, from stem cells may emanate from the lack of knowledge about mechanisms that underlie postnatal cell maturation. We characterized hepatic maturation during the postnatal day 14 (P14) to 2-month-old (M2) transition and found more than 3000 genes differentially expressed. Nearly half of such maturation genes have H3K27me3 at their promoters or gene bodies at P14 or M2. Genetic ablation of both PRC2 histone methyltransferases in perinatal livers causes hepatocytes to prematurely differentiate, expressing genes at P14 that would normally be induced later, by M2. Using srHC-seq, a new method to map sonication-resistant heterochromatin, we found that the H3K27me3+ prematurely upregulated genes have euchromatic promoters at P14. We also observed derepression of many non-hepatic lineage genes with euchromatic promoter H3K27me3-marking. Thus, Polycomb repression is used to restrain expression of late liver maturation genes and lineage inappropriate genes at euchromatic promoters.
2019-03-01 | GSE118757 | GEO
Project description:The inability to derive fully functional cell types, such as hepatocytes, from stem cells may emanate from the lack of knowledge about mechanisms that underlie postnatal cell maturation. We characterized hepatic maturation during the postnatal day 14 (P14) to 2-month-old (M2) transition and found more than 3000 genes differentially expressed. Nearly half of such maturation genes have H3K27me3 at their promoters or gene bodies at P14 or M2. Genetic ablation of both PRC2 histone methyltransferases in perinatal livers causes hepatocytes to prematurely differentiate, expressing genes at P14 that would normally be induced later, by M2. Using srHC-seq, a new method to map sonication-resistant heterochromatin, we found that the H3K27me3+ prematurely upregulated genes have euchromatic promoters at P14. We also observed derepression of many non-hepatic lineage genes with euchromatic promoter H3K27me3-marking. Thus, Polycomb repression is used to restrain expression of late liver maturation genes and lineage inappropriate genes at euchromatic promoters.
2019-03-01 | GSE119112 | GEO
Project description:PRC2 proteins EZH1 and EZH2 regulate postnatal hepatic maturation
| PRJNA488479 | ENA
Project description:PRC2 proteins EZH1 and EZH2 regulate postnatal hepatic maturation [ChIP-Seq]
| PRJNA488187 | ENA
Project description:PRC2 proteins EZH1 and EZH2 regulate postnatal hepatic maturation [RNA-Seq]
| PRJNA486739 | ENA
Project description:PRC2 proteins EZH1 and EZH2 regulate postnatal hepatic maturation [RNA-seq2]
| PRJNA516682 | ENA
Project description:PRC2 proteins EZH1 and EZH2 regulate postnatal hepatic maturation [srHC-seq]
| PRJNA488480 | ENA
Project description:BACKGROUND & AIMS:Little is known about mechanisms that underlie postnatal hepatocyte maturation and fibrosis at the chromatin level. We investigated the transcription of genes involved in maturation and fibrosis in postnatal hepatocytes of mice, focusing on the chromatin compaction the roles of the Polycomb repressive complex 2 histone methyltransferases EZH1 and EZH2. METHODS:Hepatocytes were isolated from mixed background C57BL/6J-C3H mice, as well as mice with liver-specific disruption of Ezh1 and/or Ezh2, at postnatal day 14 and 2 months after birth. Liver tissues were collected and analyzed by RNA sequencing, H3K27me3 chromatin immunoprecipitation sequencing, and sonication-resistant heterochromatin sequencing (a method to map heterochromatin and euchromatin). Liver damage was characterized by histologic analysis. RESULTS:We found more than 3000 genes differentially expressed in hepatocytes during liver maturation from postnatal day 14 to month 2 after birth. Disruption of Ezh1 and Ezh2 in livers caused perinatal hepatocytes to differentiate prematurely and to express genes at postnatal day 14 that would normally be induced by month 2 and differentiate prematurely. Loss of Ezh1 and Ezh2 also resulted in liver fibrosis. Genes with H3K27me3-postive and H3K4me3-positive euchromatic promoters were prematurely induced in hepatocytes with loss of Ezh1 and Ezh2-these genes included those that regulate hepatocyte maturation, fibrosis, and genes not specifically associated with the liver lineage. CONCLUSIONS:The Polycomb repressive complex 2 proteins EZH1 and EZH2 regulate genes that control hepatocyte maturation and fibrogenesis and genes not specifically associated with the liver lineage by acting at euchromatic promoter regions. EZH1 and EZH2 thereby promote liver homeostasis and prevent liver damage. Strategies to manipulate Polycomb proteins might be used to improve hepatocyte derivation protocols or developed for treatment of patients with liver fibrosis.
| S-EPMC6599454 | biostudies-literature