Transcriptomics

Dataset Information

3

Divergent functions of hematopoietic transcription factors in lineage priming and differentiation during erythro-megakaryopoiesis


ABSTRACT: Combinatorial actions of relatively few transcription factors control hematopoietic differentiation. To investigate this process in erythro-megakaryopoiesis, we correlated the genome-wide chromatin occupancy signatures of four master hematopoietic transcription factors (GATA1, GATA2, TAL1, and FLI1) and three diagnostic histone modification marks with the gene expression changes that occur during development of primary cultured megakaryocytes (MEG) and primary erythroblasts (ERY) from murine fetal liver hematopoietic stem/progenitor cells. We identified a robust, genome-wide mechanism of MEG-specific lineage priming by a previously described stem/progenitor cell-expressed transcription factor heptad (GATA2, LYL1, TAL1, FLI1, ERG, RUNX1, LMO2) binding to MEG-associated cis-regulatory modules (CRMs) in multipotential progenitors. This is followed by genome-wide GATA factor switching that mediates further induction of MEG-specific genes following lineage commitment. Interaction between GATA and ETS factors appears to be a key determinant of these processes. In contrast, ERY-specific lineage priming is biased toward GATA2-independent mechanisms. In addition to its role in MEG lineage priming, GATA2 plays an extensive role in late megakaryopoiesis as a transcriptional repressor at loci defined by a specific DNA signature. Our findings reveal important new insights into how ERY and MEG lineages arise from a common bipotential progenitor via overlapping and divergent functions of shared hematopoietic transcription factors. Genome-wide chromatin occupancy using ChIP-seq on 4 transcription factors (GATA1, GATA2, TAL1, and FLII) and three histone marks (H3K4me1, H3K4me3, and H3K27me3) in lineage-commited primary erythoblasts (ERY) and primary cultured megakaryocytes (MEG).

OTHER RELATED OMICS DATASETS IN: E-GEOD-49664

ORGANISM(S): Mus musculus  

SUBMITTER: Ross C Hardison   Cheryl A Keller  Tejaswini Mishra  Weisheng Wu  Dongwon Lee  Andrew V Kossenkov  Mitchell J Weiss  Michael A Beer  Christapher S Morrissey  Gerd A Blobel  Maxim Pimkin  ENCODE DCC 

PROVIDER: E-GEOD-51337 | ArrayExpress | 2014-11-14

SECONDARY ACCESSION(S): GSE51337PRJNA267254

REPOSITORIES: GEO, ArrayExpress

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Publications

Divergent functions of hematopoietic transcription factors in lineage priming and differentiation during erythro-megakaryopoiesis.

Pimkin Maxim M   Kossenkov Andrew V AV   Mishra Tejaswini T   Morrissey Christapher S CS   Wu Weisheng W   Keller Cheryl A CA   Blobel Gerd A GA   Lee Dongwon D   Beer Michael A MA   Hardison Ross C RC   Weiss Mitchell J MJ  

Genome research 20141015 12


Combinatorial actions of relatively few transcription factors control hematopoietic differentiation. To investigate this process in erythro-megakaryopoiesis, we correlated the genome-wide chromatin occupancy signatures of four master hematopoietic transcription factors (GATA1, GATA2, TAL1, and FLI1) and three diagnostic histone modification marks with the gene expression changes that occur during development of primary cultured megakaryocytes (MEG) and primary erythroblasts (ERY) from murine fet  ...[more]

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