Dataset Information


GATA-1 and heme regulate the erythroid cell transcriptome.

ABSTRACT: Alas2 gene encodes the rate-limiting enzyme in heme biosynthesis. CRISPR/Cas9-mediated ablation of two Alas2 intronic cis-elements strongly reduced GATA-1-induced Alas2 transcription, heme biosynthesis, and GATA-1 regulation of other vital constituents of the erythroid cell transcriptome. Bypassing Alas2 function in Alas2 cis-element-mutant (double mutant) cells by providing its catalytic product 5-aminolevulinic acid (5-ALA) rescued heme biosynthesis and the GATA-1-dependent genetic network. We discovered a GATA factor- and heme-dependent circuit that establishes the erythroid cell transcriptome. G1E-ER-GATA-1 WT and double mutant cells were examined. Untreated WT, beta-estradiol-treated WT, beta-estradiol-treated double-mutant, and beta-estradiol/5-ALA-treated double-mutant cells were subjected to RNA-seq.

ORGANISM(S): Mus musculus  

SUBMITTER: Colin N Dewey   Emery H Bresnick  Nobuyuki Tanimura  Kyle Hewitt 

PROVIDER: E-GEOD-74371 | ArrayExpress | 2016-01-07



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Mechanism governing heme synthesis reveals a GATA factor/heme circuit that controls differentiation.

Tanimura Nobuyuki N   Miller Eli E   Igarashi Kazuhiko K   Yang David D   Burstyn Judith N JN   Dewey Colin N CN   Bresnick Emery H EH  

EMBO reports 20151223 2

Metal ion-containing macromolecules have fundamental roles in essentially all biological processes throughout the evolutionary tree. For example, iron-containing heme is a cofactor in enzyme catalysis and electron transfer and an essential hemoglobin constituent. To meet the intense demand for hemoglobin assembly in red blood cells, the cell type-specific factor GATA-1 activates transcription of Alas2, encoding the rate-limiting enzyme in heme biosynthesis, 5-aminolevulinic acid synthase-2 (ALAS  ...[more]

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