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PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiations and Function [Cut&Run]

ABSTRACT: PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiations and Function [Cut&Run]

PROVIDER: PRJNA1053411 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27227951_1.fastq.gz	Fastqsanger.gz
	SRR27227951_2.fastq.gz	Fastqsanger.gz
	SRR27227952_1.fastq.gz	Fastqsanger.gz
	SRR27227952_2.fastq.gz	Fastqsanger.gz
	SRR27227953_1.fastq.gz	Fastqsanger.gz

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PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiations and Function [scRNA-seq]

Project description:Differential chromatin accessibility accompanies and mediates transcriptional control of diverse cell fates and their differentiation during embryogenesis. While the critical role of NKX2-1 and its transcriptional targets in lung morphogenesis and pulmonary epithelial cell differentiation is increasingly known, mechanisms by which chromatin accessibility alters the epigenetic landscape and how NKX2-1 interacts with other co-activators required for alveolar epithelial cell differentiation and function are not well understood. Here, we demonstrate that the paired domain zinc finger transcriptional regulators PRDM3 and PRDM16 regulate chromatin accessibility to mediate cell differentiation decisions during lung morphogenesis. Combined deletion of Prdm3 and Prdm16 in early lung endoderm caused perinatal lethality due to respiratory failure from loss of AT2 cell function. Prdm3/16 deletion led to the accumulation of partially differentiated AT1 cells and loss of AT2 cells. A combination of single cell RNA-seq, bulk ATAC-seq, and CUT&RUN demonstrated that PRDM3 and PRDM16 enhanced chromatin accessibility at NKX2-1 transcriptional targets in peripheral epithelial cells, with all three factors binding together at a multitude of cell-type specific cis-active DNA elements. Network analysis demonstrated that PRDM3/16 regulated genes critical for perinatal AT2 cell differentiation, surfactant homeostasis, and innate host defense. Lineage specific deletion of PRDM3/16 in AT2 cells led to lineage infidelity, with PRDM3/16 null cells acquiring a partial AT1 fate. Together, these data demonstrate that NKX2-1-dependent regulation of alveolar epithelial cell differentiations is mediated by epigenetic modulation via PRDM3/16.

2024-03-01 | GSE250365 | GEO

PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiations and Function [Cut&Run]

2024-03-01 | GSE250360 | GEO

PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiations and Function [Cut&Run H3K4me3]

2024-08-09 | GSE274355 | GEO

PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiations and Function [bulk RNA-seq]

2024-03-01 | GSE250363 | GEO

PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiations and Function [ATAC-seq]

Project description:Differential chromatin accessibility accompanies and mediates transcriptional control of diverse cell fates and their differentiation during embryogenesis. While the critical role of NKX2-1 and its transcritional targets in lung morphogenesis and pulmonary epithelial cell differentiation is increasingly known, mechanisms by which chromatin accessibility alters the epigenetic landscape to regulate NKX2-1 activites required for alveolar epithelial cell differentiation and function are not well understood. Herein, we demonstrate that the paird domain zinc finger transcriptional regulators PRDM3 and PRDM16 regulate chromatin accessibility required for NKX2-1 mediated AT1 and AT2 cell differentiation decisions during lung morphogenesis and for control of the induction of AT@ cell gene expression controlling alveolar function and ventilation at birth. PRDM3 and 16 were required for activation of AT2 cell-associated gene expression, enhancing chromatin accessibility at NKX2-1 transcriptional targets. NKX2-1, PRDM3, and PRDM16 bound together at cis-active DNA elements in AT2 and AT1 cell selective transcriptional target genes, including those critical for perinatal AT2 cell differentitaion, surfactant homeostasis, and innate host defense. Deletion of PRDM3/16 inhibited NKX2-1-dependent gene regulatory networks controlling surfactant lipid and protein production, resulting in respiratory failure at birth. NKX2-1-dependent regulation of alveolar epithelial cell differentiation is mediated by PRDM3/16.

2024-03-01 | GSE250359 | GEO

PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiations and Function

Project description:PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiations and Function

| PRJNA1053415 | ENA

PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiations and Function [Cut&Run H3K4me3]

Project description:PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiations and Function [Cut&Run H3K4me3]

| PRJNA1146039 | ENA

PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiations and Function [ATAC-seq]

Project description:PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiations and Function [ATAC-seq]

| PRJNA1053412 | ENA

PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiations and Function [scRNA-seq]

Project description:PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiations and Function [scRNA-seq]

| PRJNA1053416 | ENA

PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiations and Function [bulk RNA-seq]

Project description:PRDM3/16 Regulate Chromatin Accessibility Required for NKX2-1 Mediated Alveolar Epithelial Differentiations and Function [bulk RNA-seq]

| PRJNA1053414 | ENA

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