Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA149441 | ENA |
REPOSITORIES: ENA
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Project description:Embryonic stem cells (ESCs) maintain high genomic plasticity, essential for their capacity to enter diverse differentiation pathways. Post-transcriptional modifications of chromatin histones play a pivotal role in maintaining this plasticity. We now report that one such modification, monoubiquitylation of histone H2B on lysine 120 (H2BK120ub1), catalyzed by the E3 ligase RNF20, increases during ESC differentiation and is required for efficient execution of this process. This increase is particularly important for the transcriptional induction of long genes during ESC differentiation. Furthermore, we identify USP44 as a deubiquitinase whose downregulation by differentiation signals contributes to the increase in H2BK120ub1. Our findings suggest that optimal ESC differentiation requires dynamic changes in H2B ubiquitylation patterns, which must occur in a timely and well-coordinated manner. RNF20 depleted or control NTera2 cells stimulated with RA for 72 hours
2013-01-03 | E-GEOD-33214 | biostudies-arrayexpress
Project description:Embryonic stem cells (ESCs) maintain high genomic plasticity, essential for their capacity to enter diverse differentiation pathways. Post-transcriptional modifications of chromatin histones play a pivotal role in maintaining this plasticity. We now report that one such modification, monoubiquitylation of histone H2B on lysine 120 (H2BK120ub1), catalyzed by the E3 ligase RNF20, increases during ESC differentiation and is required for efficient execution of this process. This increase is particularly important for the transcriptional induction of long genes during ESC differentiation. Furthermore, we identify USP44 as a deubiquitinase whose downregulation by differentiation signals contributes to the increase in H2BK120ub1. Our findings suggest that optimal ESC differentiation requires dynamic changes in H2B ubiquitylation patterns, which must occur in a timely and well-coordinated manner.
2013-01-03 | GSE33214 | GEO
Project description:Rnf20 catalyzes lysine 120 mono-ubiquitination of histone H2B (H2Bub1) that has been previously invloved in normal differentiation of embryonic stem (ES) and adult stem cells. However,the mechanims underlying by which Rnf20 is recruited to its target chromosomal loci to generate H2Bub1 is still elusive. Here, we reveal that Fbxl19, a CxxC domain-containing protein, physically interacts with Rnf20, guides it preferentially to CpG island-containing target promoters, and thereby promotes mono-ubiqutination of H2B. We first show that up-regulation of Fbxl19 induces the level of global H2Bub1, while down-regulation of Fbxl19 reduces the level of H2Bub1 in mouse ES cells. Our genome-wide target mapping unveils the preferential occupancy of Fbxl19 on CpG island-containing promoters, and we further show that the binding of Fbxl19 is essential for the recruitment of Rnf20 to its target genes and subsequent H2Bub1. Altogether, our results demonstrate that Fbxl19 plays critical roles in the H2Bub1 pathway by recruiting Rnf20 to CGI target genes specifically and selectively.
2016-10-01 | GSE76569 | GEO
Project description:Rnf20 catalyzes lysine 120 mono-ubiquitination of histone H2B (H2Bub1) that has been previously involved in normal differentiation of embryonic stem (ES) and adult stem cells. However, the mechanisms underlying by which Rnf20 is recruited to its target chromosomal loci to generate H2Bub1 are still elusive. Here, we reveal that Fbxl19, a CxxC domain-containing protein, physically interacts with Rnf20, guides it preferentially to CpG island-containing target promoters, and thereby promotes mono-ubiqutination of H2B. We first show that up-regulation of Fbxl19 induces the level of global H2Bub1, while down-regulation of Fbxl19 reduces the level of H2Bub1 in mouse ES cells. Our genome-wide target mapping unveils the preferential occupancy of Fbxl19 on CpG island-containing promoters, and we further show that the binding of Fbxl19 is essential for the recruitment of Rnf20 to its target genes and subsequent H2Bub1. Altogether, our results demonstrate that Fbxl19 plays critical roles in the H2Bub1 pathway by recruiting Rnf20 to CGI target genes specifically and selectively.
2016-10-01 | GSE76558 | GEO
Project description:Neuroblastoma is an embryonic cancer that disproportionately contributes to death in young children. Sequencing data have uncovered few recurrently mutated genes in this cancer though epigenetic pathways have been implicated in disease pathogenesis. We performed a computational screen of deubiquitinating enzymes to identify potential new targets and identified the histone H2B deubiquitinating enzyme USP44 as significantly over-expressed in high-risk tumors. High levels of USP44 significantly correlate with metastatic disease, unfavorable histology, advanced patient age, and MYCN-amplification. The subset of patients with tumors expressing high levels of USP44 have a significantly worse survival, including those with tumors lacking MYCN-amplification. Depleting USP44 in neuroblastoma cell lines leads to diminished proliferation, migration, invasion, as well as impaired neuritic development in response to retinoic acid. Integrated analysis of RNA-seq and ChIP-seq demonstrates a distinct set of genes that is regulated by USP44, including those in Hallmark pathways critical to tumorigenesis – findings that were completely reversed by the re-introduction of USP44. We conclude that USP44 is a novel epigenetic regulator that restrains differentiation and promotes aggressive features. Our data further suggests that USP44 may be a novel target in this disease.
2024-06-11 | GSE262506 | GEO
Project description:Neuroblastoma is an embryonic cancer that disproportionately contributes to death in young children. Sequencing data have uncovered few recurrently mutated genes in this cancer though epigenetic pathways have been implicated in disease pathogenesis. We performed a computational screen of deubiquitinating enzymes to identify potential new targets and identified the histone H2B deubiquitinating enzyme USP44 as significantly over-expressed in high-risk tumors. High levels of USP44 significantly correlate with metastatic disease, unfavorable histology, advanced patient age, and MYCN-amplification. The subset of patients with tumors expressing high levels of USP44 have a significantly worse survival, including those with tumors lacking MYCN-amplification. Depleting USP44 in neuroblastoma cell lines leads to diminished proliferation, migration, invasion, as well as impaired neuritic development in response to retinoic acid. Integrated analysis of RNA-seq and ChIP-seq demonstrates a distinct set of genes that is regulated by USP44, including those in Hallmark pathways critical to tumorigenesis – findings that were completely reversed by the re-introduction of USP44. We conclude that USP44 is a novel epigenetic regulator that restrains differentiation and promotes aggressive features. Our data further suggests that USP44 may be a novel target in this disease.
2024-06-11 | GSE228131 | GEO
Project description:Neuroblastoma is an embryonic cancer that disproportionately contributes to death in young children. Sequencing data have uncovered few recurrently mutated genes in this cancer though epigenetic pathways have been implicated in disease pathogenesis. We performed a computational screen of deubiquitinating enzymes to identify potential new targets and identified the histone H2B deubiquitinating enzyme USP44 as significantly over-expressed in high-risk tumors. High levels of USP44 significantly correlate with metastatic disease, unfavorable histology, advanced patient age, and MYCN-amplification. The subset of patients with tumors expressing high levels of USP44 have a significantly worse survival, including those with tumors lacking MYCN-amplification. Depleting USP44 in neuroblastoma cell lines leads to diminished proliferation, migration, invasion, as well as impaired neuritic development in response to retinoic acid. Integrated analysis of RNA-seq and ChIP-seq demonstrates a distinct set of genes that is regulated by USP44, including those in Hallmark pathways critical to tumorigenesis – findings that were completely reversed by the re-introduction of USP44. We conclude that USP44 is a novel epigenetic regulator that restrains differentiation and promotes aggressive features. Our data further suggests that USP44 may be a novel target in this disease.
2024-06-11 | GSE228130 | GEO
Project description:De novo variants affecting monoubiquitination of histone H2B (H2Bub1) are enriched in human congenital heart disease. H2Bub1 is required in stem cell differentiation, cilia function, post-natal cardiomyocyte maturation, and transcriptional elongation. However, how H2Bub1 affects cardiogenesis is unknown. We show that the H2Bub1-deposition complex (RNF20-RNF40-UBE2B) is required for mouse cardiogenesis and for differentiation of human iPSCs into cardiomyocytes. Mice with cardiac-specific Rnf20 deletion are embryonic lethal and have abnormal myocardium. We then analyzed H2Bub1 marks during differentiation of human iPSCs into cardiomyocytes. H2Bub1 is erased from most genes at transition from cardiac mesoderm to cardiac progenitor cells, but is preserved on a subset of long cardiac-specific genes. When H2Bub1 is reduced in iPSC-cardiomyocytes, long cardiac-specific genes have fewer full-length transcripts. This correlates with H2Bub1 accumulation near the center of these genes. H2Bub1 accumulation near the center of tissue-specific genes was also observed in embryonic fibroblasts and fetal osteoblasts. In summary, we show that normal H2Bub1 distribution is required for cardiogenesis and cardiomyocyte differentiation, and point to H2Bub1 regulating tissue-specific gene expression by increasing the amount of full-length transcripts.
2023-10-31 | GSE246411 | GEO
Project description:De novo variants affecting monoubiquitination of histone H2B (H2Bub1) are enriched in human congenital heart disease. H2Bub1 is required in stem cell differentiation, cilia function, post-natal cardiomyocyte maturation, and transcriptional elongation. However, how H2Bub1 affects cardiogenesis is unknown. We show that the H2Bub1-deposition complex (RNF20-RNF40-UBE2B) is required for mouse cardiogenesis and for differentiation of human iPSCs into cardiomyocytes. Mice with cardiac-specific Rnf20 deletion are embryonic lethal and have abnormal myocardium. We then analyzed H2Bub1 marks during differentiation of human iPSCs into cardiomyocytes. H2Bub1 is erased from most genes at transition from cardiac mesoderm to cardiac progenitor cells, but is preserved on a subset of long cardiac-specific genes. When H2Bub1 is reduced in iPSC-cardiomyocytes, long cardiac-specific genes have fewer full-length transcripts. This correlates with H2Bub1 accumulation near the center of these genes. H2Bub1 accumulation near the center of tissue-specific genes was also observed in embryonic fibroblasts and fetal osteoblasts. In summary, we show that normal H2Bub1 distribution is required for cardiogenesis and cardiomyocyte differentiation, and point to H2Bub1 regulating tissue-specific gene expression by increasing the amount of full-length transcripts.
2023-10-31 | GSE246410 | GEO
Project description:Chromatin remodeling plays very important role in cell reprogramming, but its underlying mechanism remains poorly understood. Here, we show that RNF20 is highly expressed at the early stage of reprogramming along with the accumulation of H2B ubiquitination at the same stage, and Rnf20 knockout results in the failure of reprogramming at the initial stage but not the other two stages. RNA-seq showed that Rnf20 knockout mainly affects the early stage of cell reprogramming by impairing the transcription of MET-related genes and early pluripotency genes. Importantly, Rnf20 knockout results in a more compacted chromosomes structure in reprogrammable cells, suppressing the recruitment of reprogramming transcription factors to their proper locations on the chromosomes, and finally resulting in the failure of pluripotent gene network establishment. Our results not only uncover a previously unknown function of RNF20-mediated H2B ubiquitination in cell reprogramming, but also provide mechanistic insights into the epigenetic regulation of reprogrammable cells.
2021-02-02 | GSE165886 | GEO