Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Identification of genes regulated by Rcor1 in CD71+, TER119- erythroid progenitors using mRNA-seq analysis

ABSTRACT: Transcription cofactor Rcor1 has been linked biochemically both to neurogenesis and hematopoiesis. Here we studied the function of Rcor1 in vivo and showed it is essential to erythropoeisis during embryonic development. Rcor1 mutant proerythroblasts, unlike normal cells, can form myeloid colonies in vitro. To investigate the underlying molecular mechanisms for block of erythropoiesis and increased myeloid potential, we used RNA-seq to reveal the differentially expressed genes from erythroid progenitors due to depletion of Rcor1. RNA were extracted from FACS sorted CD71+,TER119- erythroid progenitors from control (Rcor1+/+ and Rcor1+/-) or Mutant (Rcor1-/- ) E13.5 fetal liver. Each library was made by pooling RNA from several fetal livers. Two biological replicates were made for either control or mutant condition.

ORGANISM(S): Mus musculus

SUBMITTER: Huilan Yao

PROVIDER: E-GEOD-50708 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Corepressor Rcor1 is essential for murine erythropoiesis.

Yao Huilan H Goldman Devorah C DC Nechiporuk Tamilla T Kawane Sunita S McWeeney Shannon K SK Tyner Jeffrey W JW Fan Guang G Kerenyi Marc A MA Orkin Stuart H SH Fleming William H WH Mandel Gail G

Blood 20140320 20

The corepressor Rcor1 has been linked biochemically to hematopoiesis, but its function in vivo remains unknown. We show that mice deleted for Rcor1 are profoundly anemic and die in late gestation. Definitive erythroid cells from mutant mice arrest at the transition from proerythroblast to basophilic erythroblast. Remarkably, Rcor1 null erythroid progenitors cultured in vitro form myeloid colonies instead of erythroid colonies. The mutant proerythroblasts also aberrantly express genes of the myel ...[more]

PMID: 24652990

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Project description:It is unclear how epigenetic changes regulate the induction of erythroid-specific genes during terminal erythropoiesis. Here we use global mRNA sequencing (mRNA-seq) and chromatin immunoprecipitation coupled to high-throughput sequencing (CHIP-seq) to investigate the changes that occur in mRNA levels, RNA Polymerase II (Pol II) occupancy and multiple post-translational histone modifications when erythroid progenitors differentiate into late erythroblasts. Among genes induced during this developmental transition, there was an increase in the occupancy of Pol II, the activation marks H3K4me2, H3K4me3, H3K9Ac and H4K16Ac, and the elongation methylation mark H3K79me2. In contrast, genes that were repressed during differentiation showed relative decreases in H3K79me2 levels yet had levels of Pol II binding and active histone marks similar to those in erythroid progenitors. We also found that relative changes in histone modification levels-in particular, H3K79me2 and H4K16ac-were most predictive of gene expression patterns. Our results suggest that in terminal erythropoiesis both promoter and elongation-associated marks contribute to the induction of erythroid genes, while gene repression is marked by changes in histone modifications mediating Pol II elongation. Our data maps the epigenetic landscape of terminal erythropoiesis and suggests that control of transcription elongation regulates gene expression during terminal erythroid differentiation. Mouse fetal liver cells are double-labeled for erythroid-specific TER119 and non erythroid-specific transferrin receptor (CD71) and then sorted by flow-cytometry. E14.5 fetal livers contain at least five distinct populations of cells (R1 through R5); as they progressively differentiate they gain TER119 and then gain and subsequently lose CD71. CFU-E cells and proerythroblasts make up the R1 population; R2 consists of proerythroblasts and early basophilic erythroblasts; R3 includes early and late basophilic erythroblasts; R4 is mostly polychromatophilic and orthochromatophilic erythroblasts; and R5 is comprised of late orthochromatophilic erythroblasts and reticulocytes. We have sorted for R2-R5 cells for RNA-seq experiment.

Dataset Information

Identification of genes regulated by Rcor1 in CD71+, TER119- erythroid progenitors using mRNA-seq analysis

Publications

Corepressor Rcor1 is essential for murine erythropoiesis.

Similar Datasets

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