Erythropoietin Signaling Regulates Key Epigenetic and Transcription Networks in Fetal Neural Progenitor Cells

Sollinger, Christina; Lillis, Jacquelyn; Malik, Jeffrey; Getman, Michael; Pröschel, Christoph; Steiner, Laurie A.

doi:10.1038/s41598-017-14366-0

Cited by 12 publications

(16 citation statements)

References 98 publications

(105 reference statements)

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“…Chromatin immunoprecipitation was performed as previously described 34 . In brief, 2 × 10 7 cells were washed with PBS once, then cross-linked with 1% formaldehyde for 10 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Hyperacetylated chromatin domains mark cell type-specific genes and suggest distinct modes of enhancer function

et al. 2020

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Stratification of enhancers by signal strength in ChIP-seq assays has resulted in the establishment of super-enhancers as a widespread and useful tool for identifying cell type-specific, highly expressed genes and associated pathways. We examine a distinct method of stratification that focuses on peak breadth, termed hyperacetylated chromatin domains (HCDs), which classifies broad regions exhibiting histone modifications associated with gene activation. We find that this analysis serves to identify genes that are both more highly expressed and more closely aligned to cell identity than super-enhancer analysis does using multiple data sets. Moreover, genetic manipulations of selected gene loci suggest that some enhancers located within HCDs work at least in part via a distinct mechanism involving the modulation of histone modifications across domains and that this activity can be imported into a heterologous gene locus. In addition, such genetic dissection reveals that the super-enhancer concept can obscure important functions of constituent elements.

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Section: Methodsmentioning

confidence: 99%

Hyperacetylated chromatin domains mark cell type-specific genes and suggest distinct modes of enhancer function

et al. 2020

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“…Primers for qPCR are listed in online supplementary table 1. ChIP was done on formalin-fixed, paraffin-embedded sections using a protocol modified from Fanelli et al 21 and Sollinger et al 22 and antibody against H3K27Ac (Abcam). Primers used for ChIP-qPCR studies are listed in online supplementary file 1.…”

Section: Methodsmentioning

confidence: 99%

Disruption of normal patterns of FOXF1 expression in a lethal disorder of lung development

et al. 2019

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BackgroundAlveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) is a lethal disorder of lung development. ACDMPV is associated with haploinsufficiency of the transcription factor FOXF1, which plays an important role in the development of the lung and intestine. CNVs upstream of the FOXF1 gene have also been associated with an ACDMPV phenotype, but mechanism(s) by which these deletions disrupt lung development are not well understood. The objective of our study is to gain insights into the mechanisms by which CNVs contribute to an ACDMPV phenotype.MethodsWe analysed primary lung tissue from an infant with classic clinical and histological findings of ACDMPV and harboured a 340 kb deletion on chromosome 16q24.1 located 250 kb upstream of FOXF1.ResultsIn RNA generated from paraffin-fixed lung sections, our patient had lower expression of FOXF1 than age-matched controls. He also had an abnormal pattern of FOXF1 protein expression, with a dramatic loss of FOXF1 expression in the lung. To gain insights into the mechanisms underlying these changes, we assessed the epigenetic landscape using chromatin immunoprecipitation, which demonstrated loss of histone H3 lysine 27 acetylation (H3K27Ac), an epigenetic mark of active enhancers, in the region of the deletion.ConclusionsTogether, these data suggest that the deletion disrupts an enhancer responsible for directing FOXF1 expression in the developing lung and provide novel insights into the mechanisms underlying a fatal developmental lung disorder.

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“…For ChIPmentation, libraries were prepared as outlined in [21]. Briefly, chromatin immunoprecipitation was done using 1-5 × 10 5 cells, as outlined in [44]. Following immunoprecipitation using H3K27me3 (Cell Signaling Technology, 9733S) or NFYB antibody (Diagenode, C1540241), tagmentation was done using transposase (Nextera, Illumina), followed by elution from magnetic beads.…”

Section: Library Construction: Atac-seq and Chipmentationmentioning

confidence: 99%

The histone methyltransferase Setd8 alters the chromatin landscape and regulates the expression of key transcription factors during erythroid differentiation

Myers

Couch

Murphy

et al. 2020

Epigenetics & Chromatin

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Background: SETD8 is the sole methyltransferase capable of mono-methylating histone H4, lysine 20. SETD8 and H4K20me1 play a role in a number of essential biologic processes, including cell cycle progression, establishment of higher order chromatin structure, and transcriptional regulation. SETD8 is highly expressed in erythroid cells and erythroid deletion of Setd8 is embryonic lethal by embryonic day 11.5 (E11.5) due to profound anemia, suggesting that it has an erythroid-specific function. The function of SETD8 in the hemopoietic system is poorly understood. The goal of our study was to gain insights into the function of SETD8 during erythroid differentiation. Results:We performed ATAC-seq (assay for transposase-accessible chromatin) on sorted populations of E10.5 Setd8 mutant and control erythroblasts. Accessibility profiles were integrated with expression changes and a mark of heterochromatin (H3K27me3) performed in wild-type E10.5 erythroblasts to further understand the role of SETD8 in erythropoiesis. Data integration identified regions of greater chromatin accessibility in Setd8 mutant cells that colocated with H3K27me3 in wild-type E10.5 erythroblasts suggesting that these regions, and their associated genes, are repressed during normal erythropoiesis. The majority of these more accessible regions were located in promoters and they frequently co-located with the NFY complex. Pathway analysis of genes identified through data integration revealed stemness-related pathways. Among those genes were multiple transcriptional regulators active in multipotent progenitors, but repressed during erythroid differentiation including Hhex, Hlx, and Gata2. Consistent with a role for SETD8 in erythroid specification, SETD8 expression is up-regulated upon erythroid commitment, and Setd8 disruption impairs erythroid colony forming ability. Conclusion:Taken together, our results suggest that SETD8 is an important regulator of the chromatin landscape during erythroid differentiation, particularly at promoters. Our results also identify a novel role for Setd8 in the establishment of appropriate patterns of lineage-restricted gene expression during erythroid differentiation.

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Erythropoietin Signaling Regulates Key Epigenetic and Transcription Networks in Fetal Neural Progenitor Cells

Cited by 12 publications

References 98 publications

Hyperacetylated chromatin domains mark cell type-specific genes and suggest distinct modes of enhancer function

Hyperacetylated chromatin domains mark cell type-specific genes and suggest distinct modes of enhancer function

Disruption of normal patterns of FOXF1 expression in a lethal disorder of lung development

The histone methyltransferase Setd8 alters the chromatin landscape and regulates the expression of key transcription factors during erythroid differentiation

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