LncRNA DEANR1 facilitates human endoderm differentiation by activating FOXA2 expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE44875 | GEO | 2014/06/01
SECONDARY ACCESSION(S): PRJNA192215
REPOSITORIES: GEO
Similar Datasets
Project description:Foxa2 is required for endoderm differentiation into hepatic lineage. The mechanism of activation for Foxa2 during this developmental process has not been elucidated yet. We established an in vitro system to guide ES cells differentiating into definitive endoderm (DE) cells and the following DE cells to early hepatic cells. ChIP-seq assays have been successfully performed to assess Foxa2 binding profile. Over 50% of Foxa2 target genes in DE cells were found being activated in hepatic cells which were at a stage later than DE stage. Therefore, our finding at genome-wide level proved Foxa2 serving as a pioneer factor at DE stage. Furthermore, Foxa2 could specifically induce H3K4me2 modifications to the promoter/enhancer regions of many hepatic genes to pre-mark the chromatin, and determine the hepatic lineage differentiation competence. Our study illustrated the wide existence of Foxa2M-bM-^@M-^Ys pioneer factor function and uncovered the correlation between pioneer factor and chromatin pre-mark. These findings will be helpful for understanding the developmental process of hepatogenesis and efficiently controlling Foxa2 during hepatic induction for generating functional hepatocytes. Examination of Foxa2 binding sites in mESC-derived DE cells
2012-08-29 | E-GEOD-40423 | biostudies-arrayexpress
Project description:Foxa2 is required for endoderm differentiation into hepatic lineage. The mechanism of activation for Foxa2 during this developmental process has not been elucidated yet. We established an in vitro system to guide ES cells differentiating into definitive endoderm (DE) cells and the following DE cells to early hepatic cells. ChIP-seq assays have been successfully performed to assess Foxa2 binding profile. Over 50% of Foxa2 target genes in DE cells were found being activated in hepatic cells which were at a stage later than DE stage. Therefore, our finding at genome-wide level proved Foxa2 serving as a pioneer factor at DE stage. Furthermore, Foxa2 could specifically induce H3K4me2 modifications to the promoter/enhancer regions of many hepatic genes to pre-mark the chromatin, and determine the hepatic lineage differentiation competence. Our study illustrated the wide existence of Foxa2’s pioneer factor function and uncovered the correlation between pioneer factor and chromatin pre-mark. These findings will be helpful for understanding the developmental process of hepatogenesis and efficiently controlling Foxa2 during hepatic induction for generating functional hepatocytes.
2012-08-29 | GSE40423 | GEO
Project description:Long non-coding RNAs (lncRNAs) play important roles in the regulation of many biological processes in the cell like transcription, translation, splicing, transport, etc. More than 10K lncRNAs are predicted in human, but functions for the majority remain unknown. LncRNAs may contribute to the development of multiple diseases that makes them perspective diagnostic and prognostic markers as well as drug targets [1]. Murine lncRNA Falcor/LL35 is a proposed functional analog of human lncRNA DEANR1, which is predominantly expressed in murine lungs and liver, intestine and pancreas [2, 3]. While the participation of LL35 in LL35–Foxa2 (transcription factor) regulatory loop during regeneration after lung injury was previously described by Swarr et al. [2], its functional role in murine liver remains unknown. In our work we focused on revealing the role of murine lncRNA LL35 in hepatocytes and in mouse liver. We analyzed changes in proteome of AML12 (normal hepatocytes) cell line on the 2nd day after LL35 depletion. [1] Morlando, M., Ballarino, M., & Fatica, A. (2015). Long non-coding RNAs: New players in hematopoiesis and leukemia. Frontiers in Medicine, Vol. 2. [2] Swarr, D. T., Herriges, M., Li, S., Morley, M., Fernandes, S., Sridharan, A., … Morrisey, E. E. (2019). The long noncoding RNA Falcor regulates Foxa2 expression to maintain lung epithelial homeostasis and promote regeneration. Genes & Development, 33(11-12), 656–668. [3] Sergeeva, O. V, Korinfskaya, S. A., Kurochkin, I. I., & Zatsepin, T. S. (2019). Long Noncoding RNA LL35 / Falcor Regulates Expression of Transcription Factor Foxa2 in Hepatocytes in Normal and Fibrotic Mouse Liver. Acta Naturae, 11(42), 66–74.
2022-08-11 | PXD033910 | Pride
Project description:Many long non-coding RNA (lncRNA) species have been identified in mammalian cells, but the genomic origin, regulation and function of these molecules in individual cell types is poorly understood. We have generated comprehensive catalogs of lncRNA species expressed in human and murine embryonic stem cells (ESCs) and mapped their genomic origin. A surprisingly large fraction of these transcripts (>60%) originate from divergent transcription at promoters of active protein-coding genes. The divergently transcribed lncRNA/mRNA gene pairs exhibit coordinated changes in transcription when ESCs are differentiated into endoderm. A significant number of the divergently transcribed lncRNAs/mRNA pairs are conserved between human and mouse ESCs. Disruption of promoter-associated lncRNA orthologs in a zebrafish model of early development causes gross developmental defects. Our results reveal that transcription of most lncRNA genes is coordinated with transcription of protein-coding genes and that these lncRNAs have roles in early development. Analysis of genome-wide lncRNA transcription in human embryonic stem cells and early differentiation using RNA-seq, GRO-seq and ChIP-seq
2013-01-02 | E-GEOD-41009 | biostudies-arrayexpress
Project description:Background: The Spemann/Mangold organizer is a transient tissue critical for patterning the gastrula stage vertebrate embryo and formation of the three germ layers. Despite its important role during development, there are still relatively few genes with specific expression in the organizer and its derivatives. Foxa2 is a forkhead transcription factor that is absolutely required for formation of the mammalian equivalent of the organizer, the node, the axial mesoderm and the definitive endoderm (DE). However, the targets of Foxa2 during embryogenesis, and the molecular impact of organizer loss on the gastrula embryo, have not been well defined. Results: To identify genes specific to the Spemann/Mangold organizer, we performed a microarray-based screen that compared wild-type and Foxa2 mutant embryos at late gastrulation stage (E7.5). We could detect genes that were consistently down-regulated in replicate pools of mutant embryos versus wild-type, and these included a number of known node and DE markers. We selected 314 genes without previously published data at E7.5 and screened for expression by whole mount in situ hybridization. We identified 10 novel expression patterns in the node and 5 in the definitive endoderm. We also found significant reduction of markers expressed in secondary tissues that require interaction with the organizer and its derivatives, such as cardiac mesoderm, vasculature, primitive streak, and anterior neuroectoderm. Conclusions: The genes identified in this screen represent novel Spemann/Mangold organizer genes as well as potential Foxa2 targets. Further investigation will be needed to define these genes as novel developmental regulatory factors involved in organizer formation and function. We have placed these genes in a Foxa2-dependent genetic regulatory network and we hypothesize how Foxa2 may regulate a molecular program of Spemann/Mangold organizer development. We have also shown how early loss of the organizer and its inductive properties in an otherwise normal embryo, impacts on the molecular profile of surrounding tissues.
2008-10-31 | GSE5424 | GEO
Project description:Pioneer transcription factors (PTF) can recognize their binding sites on nucleosomal DNA and trigger chromatin opening for recruitment of other non-pioneer transcription factors. However, critical properties of PTFs are still poorly understood, such as how can these transcription factors selectively recognize cell type-specific binding sites and under which conditions can they initiate chromatin remodelling. Here we show that early endoderm binding sites of the paradigm PTF Foxa2 are epigenetically primed by low levels of active chromatin modifications in embryonic stem cells (ESC). Priming of these binding sites is supported by preferential recruitment of Foxa2 to endoderm binding sites compared to lineage-inappropriate binding sites, when ectopically expressed in ESCs. We further show that binding of Foxa2 is required for chromatin opening during endoderm differentiation. However, increased chromatin accessibility was only detected on binding sites which are synergistically bound with other endoderm transcription factors. Thus, our data suggest that binding site selection of PTFs is directed by the chromatin environment and that chromatin opening requires collaboration of PTFs with additional transcription factors.
2019-07-26 | GSE116255 | GEO
Project description:Pioneer transcription factors (PTF) can recognize their binding sites on nucleosomal DNA and trigger chromatin opening for recruitment of other non-pioneer transcription factors. However, critical properties of PTFs are still poorly understood, such as how can these transcription factors selectively recognize cell type-specific binding sites and under which conditions can they initiate chromatin remodelling. Here we show that early endoderm binding sites of the paradigm PTF Foxa2 are epigenetically primed by low levels of active chromatin modifications in embryonic stem cells (ESC). Priming of these binding sites is supported by preferential recruitment of Foxa2 to endoderm binding sites compared to lineage-inappropriate binding sites, when ectopically expressed in ESCs. We further show that binding of Foxa2 is required for chromatin opening during endoderm differentiation. However, increased chromatin accessibility was only detected on binding sites which are synergistically bound with other endoderm transcription factors. Thus, our data suggest that binding site selection of PTFs is directed by the chromatin environment and that chromatin opening requires collaboration of PTFs with additional transcription factors.
2019-07-26 | GSE116259 | GEO
Project description:Pioneer transcription factors (PTF) can recognize their binding sites on nucleosomal DNA and trigger chromatin opening for recruitment of other non-pioneer transcription factors. However, critical properties of PTFs are still poorly understood, such as how can these transcription factors selectively recognize cell type-specific binding sites and under which conditions can they initiate chromatin remodelling. Here we show that early endoderm binding sites of the paradigm PTF Foxa2 are epigenetically primed by low levels of active chromatin modifications in embryonic stem cells (ESC). Priming of these binding sites is supported by preferential recruitment of Foxa2 to endoderm binding sites compared to lineage-inappropriate binding sites, when ectopically expressed in ESCs. We further show that binding of Foxa2 is required for chromatin opening during endoderm differentiation. However, increased chromatin accessibility was only detected on binding sites which are synergistically bound with other endoderm transcription factors. Thus, our data suggest that binding site selection of PTFs is directed by the chromatin environment and that chromatin opening requires collaboration of PTFs with additional transcription factors.
2019-07-26 | GSE116261 | GEO
Project description:LncRNA DEANR1 facilitates human endoderm differentiation by activating FOXA2 expression
| PRJNA192215 | ENA
Project description:Foxa2 is required for endoderm differentiation into the hepatic lineage. The mechanism of activation for Foxa2 during this developmental process has not been elucidated yet. We established an in vitro system to guide ES cells differentiating into definitive endoderm (DE) cells and the following DE cells to early hepatic cells. ChIP-seq assays have been successfully performed to assess the Foxa2 binding profile. Over 50% of Foxa2 target genes in DE cells were found to be activated in hepatic cells which were at a stage later than the DE stage. Therefore, our finding at the genome-wide level proved Foxa2 serves as a pioneer factor at the DE stage. Furthermore, Foxa2 could specifically induce H3K4me2 modifications to the promoter/enhancer regions of many hepatic genes to pre-mark the chromatin, and determine the hepatic lineage differentiation competence. Our study illustrated the wide existence of Foxa2's pioneer factor function and uncovered the correlation between pioneer factor and chromatin pre-mark. These findings will be helpful for understanding the developmental process of hepatogenesis and efficiently controlling Foxa2 during hepatic induction for generating functional hepatocytes. To further gain a genome-wide view of Foxa2's effects on its target gene expression, 3 representative time points from the ES cell differentiation process to hepatic cells were selected for cDNA microarray analysis: 1) Day 0, representing ES cells, where there was no Foxa2 expression; 2) Day 5, representing DE cells; and 3) Day 7, representing early hepatic cells.
2012-08-02 | E-GEOD-39854 | biostudies-arrayexpress