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Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis [ATAC-seq]

ABSTRACT: To determine hemogen function in chromatin accessbility, ATAC Seq was performed in both WT and hemogen KO mouse liver. Loss of hemogen caused generally decresed of chrmoatin accessbility on the hemogen/BRG1 binding promoter and enhancer .

ORGANISM(S): Mus musculus

PROVIDER: GSE184553 | GEO | 2022/03/21

REPOSITORIES: GEO

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Hemogen/BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis.

Project description:Hemogen is a hematopoietic tissue-specific gene that regulates the proliferation and differentiation of hematopoietic cells; however, the mechanism underlying its function in erythropoiesis is unknown. We found that depletion of hemogen in human CD34+ erythroid progenitor cells and HUDEP2 cells significantly reduced the expression of genes associated with heme and hemoglobin synthesis, supporting a positive role for hemogen in erythroid maturation. In human K562 cells, hemogen antagonized the occupancy of corepressors nucleosome remodeling and histone deacetylase (NuRD) complex and facilitated LDB1 complex-mediated chromatin looping. Hemogen recruited SWI/SNF complex ATPase BRG1 as a coactivator to regulate nucleosome accessibility and H3K27ac enrichment for promoter and enhancer activity. To determine whether hemogen/BRG1 cooperativity is conserved in mammalian systems, we generated hemogen-knockout/knockin mice and investigated hemogen/BRG1 function in murine erythropoiesis. Loss of hemogen in embryonic days 12.5 to 16.5 fetal liver cells impeded erythroid differentiation through reducing the production of mature erythroblasts. Chromatin immunoprecipitation sequencing in wild-type and hemogen-knockout animals revealed that BRG1 is largely dependent on hemogen to regulate chromatin accessibility at erythroid gene promoters and enhancers. In summary, the hemogen/BRG1 interaction in mammals is essential for fetal erythroid maturation and hemoglobin production through its active role in promoter and enhancer activity and chromatin organization.

| S-EPMC9203704 | biostudies-literature

Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis [ChIP-seq]

Project description:To determine hemogen function in regulatory elements, ChIPmentation was performed in both WT and hemogen KO K562 cells and H3K27ac enrichment was significantly reduced at both promoters and enhancers in loss of hemogen. To identify direct targets and the regulatory role of hemogen in murine erythroid gene expression, hemogen and BRG1 ChIP-seq was performed in the WT and hemogen KO E14.5 fetal liver cells. Hemogen was found enriched in GATA1/TAL1 binding motifs and equally bind to the promoter and potential enhancer region. Notably, BRG1 occupancy (95%) was almost completely coincident with hemogen binding sites and loss of hemogen greatly impaired the BRG1 occupancy at both erythroid promoters and enhancers.

2022-03-21 | GSE184605 | GEO

Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis [ATAC-seq]

Project description:Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis [ATAC-seq]

| PRJNA765025 | ENA

Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis

Project description:Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis

| PRJNA765349 | ENA

Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-03-21 | GSE184606 | GEO

Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis [RNA-seq]

Project description:Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis [RNA-seq]

| PRJNA765029 | ENA

Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis [ChIP-seq]

Project description:Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis [ChIP-seq]

| PRJNA765350 | ENA

Hemogen /BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis [RNA-seq]

Project description:To gain insight into hemogen function during human erythropoiesis, RNA-seq was performed in different type of erythroid cells, such as WT and hemogen KD CD34+ cells, WT and hemogen KD HUDEP2 cells, WT and hemogen KO K562 cells. Notably, depletion of hemogen in these human erythroid cells significantly reduced the expression of genes associated with heme and hemoglobin synthesis, such as ALAS2, HMBS, GYPA, EPOR, and HBB, supporting a positive role of hemogen in erythroid maturation. To further explore hemogen function in mouse embryonic erythropoiesis, RNA-seq was performed in WT and hemogen KO E14.5 fetal liver cells and the data indicated hemogen play a consistently positive role in erythroid maturation-related genes as shown in the human cells, suggested hemogen is conserved activator during the mammalian erythropoiesis.

2022-03-21 | GSE184558 | GEO

Brg1 activates enhancer repertoires to establish B cell identity and modulate cell growth

Project description:Early B cell development is orchestrated by the combined activities of the transcriptional regulators E2A, EBF1, Foxo1 and Ikaros. However, how the genome-wide binding patterns of these regulators are modulated during B-lineage development remains to be determined. Here, we found that in lymphoid progenitors the chromatin remodeler Brg1 specified the B cell fate. In committed pro-B cells Brg1 regulated Igh locus contraction and controlled c-Myc expression to modulate the expression of genes that regulate ribosome biogenesis. In committed pro-B cells Brg1 also suppressed a pre-B lineage-specific pattern of gene expression. Finally, we found that Brg1 acted mechanistically to establish B cell fate and modulate cell growth by facilitating access of lineage-specific transcription factors to poised enhancer repertoires. 8 ATAC-Seq samples from sorted ALP and BLP (duplicates, control and Brg1-deleted), 4 ATAC-Seq samples from cultured pro-B cells (duplicates, control and Brg1-deleted), 2 Ikaros ChIP-seq samples (performed in Rag1-/- pro-B cells and in E2A-/- pre-pro-B cells), 1 Brg1 ChIP-seq sample and accompanying Input sample (both in Rag1-/- pro-B cells), 4 RNA-Seq samples from cultured pro-B cells (duplicates, control and Brg1-deleted), 6 RNA-Seq samples from cultured Rag1-/- pro-B cells (triplicates, control and Brg1-knock down).

2015-05-15 | E-GEOD-66978 | biostudies-arrayexpress

Brg1 Modulates Enhancer Activation and Polycomb-mediated Repression in Mesoderm Differentiation [ChIP-exo]

Project description:We investigated the genome-wide occupancy changes in normal and Brg1-deleted mesoderm differentiation of mouse embryonic stem cells of chromatin regulators and histone modifications. ChIP exo for BRG1 in 2 conditions: Day4 THF (Control) and Day4 4OHT (Brg1-deleted). 1-2 replicates per condition.

2015-03-01 | E-GEOD-63976 | biostudies-arrayexpress

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