ArticleEMBO reports2016
Mechanism governing heme synthesis reveals a GATA factor/heme circuit that controls differentiation.
Article in EMBO reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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Who cites it
54 citing papers in PubMed, 83 citations in OpenAlex.
- Article
- A reversible feedback mechanism regulating mitochondrial heme synthesis.The Journal of biological chemistry · 2026Article
- A reversible feedback mechanism regulating mitochondrial heme synthesis.bioRxiv : the preprint server for biology · 2025Article
- KDM4C works in concert with GATA1 to regulate heme metabolism in head and neck squamous cell carcinoma.Cellular and molecular life sciences : CMLS · 2025Article
- CRISPR/Cas9-based editing of NF-YC4 promoters yields high-protein rice and soybean.The New phytologist · 2025Article
- The Multifaceted Roles of BACH1 in Disease: Implications for Biological Functions and Therapeutic Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Erythropoiesis: insights from a genomic perspective.Experimental & molecular medicine · 2024Review
- Endogenous small molecule effectors in GATA transcription factor mechanisms governing biological and pathological processes.Experimental hematology · 2024Review
- Key GenesGenes · 2024Article
- Quantitative analysis of heme and hemoglobin for the detection of intravascular hemolysis.Analytica chimica acta · 2024Article
- Spatiotemporal expression and control of haemoglobin in space.Nature communications · 2024Article
- Increased iron uptake by splenic hematopoietic stem cells promotes TET2-dependent erythroid regeneration.Nature communications · 2024Article
- A transcriptional network governing ceramide homeostasis establishes a cytokine-dependent developmental process.Nature communications · 2023Article
- Pathogenic human variant that dislocates GATA2 zinc fingers disrupts hematopoietic gene expression and signaling networks.The Journal of clinical investigation · 2023Article
- RNA-regulatory exosome complex suppresses an apoptotic program to confer erythroid progenitor cell survival in vivo.Blood advances · 2023Article
- Heme-dependent induction of mitophagy program during differentiation of murine erythroid cells.Experimental hematology · 2023Article
- G-quadruplexes sense natural porphyrin metabolites for regulation of gene transcription and chromatin landscapes.Genome biology · 2022Article
- HDAC1 and PRC2 mediate combinatorial control in SPI1/PU.1-dependent gene repression in murine erythroleukaemia.Nucleic acids research · 2022Article
- Heme as a differentiation-regulatory transcriptional cofactor.International journal of hematology · 2022Review
- Congenital sideroblastic anemia model due to ALAS2 mutation is susceptible to ferroptosis.Scientific reports · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
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-2). Using genetic editing to unravel mechanisms governing heme biosynthesis, we discovered a GATA factor- and heme-dependent circuit that establishes the erythroid cell transcriptome. CRISPR/Cas9-mediated ablation of two Alas2 intronic cis elements strongly reduces GATA-1-induced Alas2 transcription, heme biosynthesis, and surprisingly, GATA-1 regulation of other vital constituents of the erythroid cell transcriptome. Bypassing ALAS-2 function in Alas2 cis element-mutant cells by providing its catalytic product 5-aminolevulinic acid rescues heme biosynthesis and the GATA-1-dependent genetic network. Heme amplifies GATA-1 function by downregulating the heme-sensing transcriptional repressor Bach1 and via a Bach1-insensitive mechanism. Through this dual mechanism, heme and a master regulator collaborate to orchestrate a cell type-specific transcriptional program that promotes cellular differentiation.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.