Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Synergism between PPARα and glucocorticoid receptor signaling promotes self-renewal of BFU-E erythroid progenitors and increases red cell production

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Xiaofei Gao

PROVIDER: E-GEOD-63837 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

PPAR-α and glucocorticoid receptor synergize to promote erythroid progenitor self-renewal.

Lee Hsiang-Ying HY Gao Xiaofei X Barrasa M Inmaculada MI Li Hu H Elmes Russell R RR Peters Luanne L LL Lodish Harvey F HF

Nature 20150511 7557

Many acute and chronic anaemias, including haemolysis, sepsis and genetic bone marrow failure diseases such as Diamond-Blackfan anaemia, are not treatable with erythropoietin (Epo), because the colony-forming unit erythroid progenitors (CFU-Es) that respond to Epo are either too few in number or are not sensitive enough to Epo to maintain sufficient red blood cell production. Treatment of these anaemias requires a drug that acts at an earlier stage of red cell formation and enhances the formatio ...[more]

PMID: 25970251

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Project description:Hematopoiesis is a well-established model system to study molecular mechanisms of lineage-specific differentiation. Key transcription factors (TFs), such as PU.1, NF-E2 and GATA1 are implicated in crucial aspects of distinct hematopoietic lineages. How TFs collaborate with histone modificatons and how they affect the chromatin status remains to be elucidated. Chromatin-Immunoprecipitation followed by next-generation sequencing (ChIP-seq) has been proven to be an excellent tool to study chromatin modifications genome-wide. In this study, ChIP-seq was used to investigate the H3K4me2 landscape at enhancers during hematopoietic differentiation, starting from the hematopoietic stem cell (HSC) up to the fully differentiated erythrocyte, megakaryocyte or granulocyte. Although cell morphology and gene expression profiles differ extensively in committed erythrocytes, megakaryocytes and granulocytes, the genomic landscape of H3K4me2 is surprisingly alike across the three cell types. Granulocytes, in particular, seem to display an ‘erythocyte-like’ chromatin pattern. Similar results were observed for another chromatin mark, H3K27ac. Unexpectedly, the common progenitors of erythrocytes and granulocytes do not display a similar chromatin pattern, excluding the idea that the H3K4me2 mark is placed early on during differentiation. These results also suggest that the chromatin state is probably not the determining factor for lineage differentiation, but that rather lineage specific TF binding is important. In agreement with this, mature megakaryocytes loose the H3K4me2 mark surrounding erythrocyte-specific genes. This might be explained because megakaryocytes and erythrocytes both express the lineage specific TFs GATA1 and NF-E2. Altogether, we show that committed granulocytes and erythrocytes display similar H3K4me2 and H3K27ac patterns, and that those marks alone cannot predict which genes will be expressed eventually. Genomic ChIP-Seq on key transcription factors and histone modification marks in hematopoiesis

Dataset Information

Synergism between PPARα and glucocorticoid receptor signaling promotes self-renewal of BFU-E erythroid progenitors and increases red cell production

Publications

PPAR-α and glucocorticoid receptor synergize to promote erythroid progenitor self-renewal.

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