Abstract:
:Mitoferrin 1 (Mfrn1; Slc25a37) and mitoferrin 2 (Mfrn2; Slc25a28) function as essential mitochondrial iron importers for heme and Fe/S cluster biogenesis. A genetic deficiency of Mfrn1 results in a profound hypochromic anemia in vertebrate species. To map the cis-regulatory modules (CRMs) that control expression of the Mfrn genes, we utilized genome-wide chromatin immunoprecipitation (ChIP) datasets for the major erythroid transcription factor GATA-1. We identified the CRMs that faithfully drive the expression of Mfrn1 during blood and heart development and Mfrn2 ubiquitously. Through in vivo analyses of the Mfrn-CRMs in zebrafish and mouse, we demonstrate their functional and evolutionary conservation. Using knockdowns with morpholinos and cell sorting analysis in transgenic zebrafish embryos, we show that GATA-1 directly regulates the expression of Mfrn1. Mutagenesis of individual GATA-1 binding cis elements (GBE) demonstrated that at least two of the three GBE within this CRM are functionally required for GATA-mediated transcription of Mfrn1. Furthermore, ChIP assays demonstrate switching from GATA-2 to GATA-1 at these elements during erythroid maturation. Our results provide new insights into the genetic regulation of mitochondrial function and iron homeostasis and, more generally, illustrate the utility of genome-wide ChIP analysis combined with zebrafish transgenesis for identifying long-range transcriptional enhancers that regulate tissue development.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Amigo JD,Yu M,Troadec MB,Gwynn B,Cooney JD,Lambert AJ,Chi NC,Weiss MJ,Peters LL,Kaplan J,Cantor AB,Paw BHdoi
10.1128/MCB.01010-10subject
Has Abstractpub_date
2011-04-01 00:00:00pages
1344-56issue
7eissn
0270-7306issn
1098-5549pii
MCB.01010-10journal_volume
31pub_type
杂志文章abstract::We have developed a system to study mutations that affect xanthine-guanine phosphoribosyltransferase gene (gpt) expression in hypoxanthine-guanine phosphoribosyltransferase-deficient CHO cells that have been transformed by the plasmid vector pSV2gpt. One isolated transformant, designated AS52, carries a single copy of...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.7.1411
更新日期:1984-07-01 00:00:00
abstract::Despite the identification of PBC proteins as cofactors that provide DNA affinity and binding specificity for the HOX homeodomain proteins, HOX proteins do not demonstrate robust activity in transient-transcription assays and few authentic downstream targets have been identified for these putative transcription factor...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.21.7509-7522.2001
更新日期:2001-11-01 00:00:00
abstract::Protein ubiquitination provides an efficient and reversible mechanism to regulate cell cycle progression and checkpoint control. Numerous regulatory proteins direct the addition of ubiquitin to lysine residues on target proteins, and these are countered by an army of deubiquitinating enzymes (DUBs). BRCA1-associated p...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01517-08
更新日期:2009-04-01 00:00:00
abstract::Compromised immunoregulation contributes to obesity and complications in metabolic pathogenesis. Here, we demonstrate that the nuclear factor of activated T cell (NFAT) group of transcription factors contributes to glucose and insulin homeostasis. Expression of two members of the NFAT family (NFATc2 and NFATc4) is ind...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00580-06
更新日期:2006-10-01 00:00:00
abstract::During Xenopus development, the synthesis of ribosomal proteins is regulated at the translational level. To identify the region of the ribosomal protein mRNAs responsible for their typical translational behavior, we constructed a fused gene in which the upstream sequences (promoter) and the 5' untranslated sequence (f...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.2.816
更新日期:1990-02-01 00:00:00
abstract::Phosphorylation is one of the key mechanisms that regulate centrosome biogenesis, spindle assembly, and cell cycle progression. However, little is known about centrosome-specific phosphorylation sites and their functional relevance. Here, we identified phosphoproteins of intact Drosophila melanogaster centrosomes and ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00814-12
更新日期:2012-09-01 00:00:00
abstract::Nuclear expression and consequent biological action of the eukaryotic NF-kappa B transcription factor complex are tightly regulated through its cytoplasmic retention by an ankyrin-rich inhibitory protein termed I kappa B alpha. I kappa B alpha specifically binds to and masks the nuclear localization signal of the RelA...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.3.1058
更新日期:1996-03-01 00:00:00
abstract::The elongation of transcription is a highly regulated process that requires negative and positive effectors. By binding the double-stranded stem in the transactivation response (TAR) element, RD protein from the negative transcription elongation factor (NELF) inhibits basal transcription from the long terminal repeat ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.2.787-795.2004
更新日期:2004-01-01 00:00:00
abstract::The receptors for thyroid hormone (T3R), all-trans-retinoic acid (RAR), and 9-cis-retinoic acid (RXR) bind DNA response elements as homo- and heterodimers. The ligand-binding domains of these receptors contain nine conserved heptads proposed to play a role in dimerization. Mutant receptors with changes in the first or...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.9.5725
更新日期:1993-09-01 00:00:00
abstract::Overexpression of the nuclear receptor 4A1 (NR4A1) in breast cancer patients is a prognostic factor for decreased survival and increased metastasis, and this has been linked to NR4A1-dependent regulation of transforming growth factor β (TGF-β) signaling. Results of RNA interference studies demonstrate that basal migra...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00912-15
更新日期:2016-04-15 00:00:00
abstract::Autophosphorylated growth factor receptors provide binding sites for the src homology 2 domains of intracellular signaling molecules. In response to epidermal growth factor (EGF), the activated EGF receptor binds to a complex containing the signaling protein GRB2 and the Ras guanine nucleotide-releasing factor Sos, le...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.1.509
更新日期:1994-01-01 00:00:00
abstract::U6 is the most conserved of the five small nuclear RNAs known to participate in pre-mRNA splicing. In the fission yeast Schizosaccharomyces pombe, the single-copy gene encoding this RNA is itself interrupted by an intron (T. Tani and Y. Ohshima, Nature (London) 337:87-90, 1989). Here we report analysis of the U6 genes...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.10.5548
更新日期:1990-10-01 00:00:00
abstract::The gene encoding the testis isozyme of angiotensin-converting enzyme (testis ACE) is one example of the many genes expressed uniquely during spermatogenesis. This protein is expressed by developing germ cells late in their development and results from the activation of a sperm-specific promoter that is located within...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.1.18
更新日期:1993-01-01 00:00:00
abstract::Genomic instability, including the ability to undergo gene amplification, is a hallmark of neoplastic cells. Similar to normal cells, "nonpermissive" REF52 cells do not develop resistance to N-(phosphonacetyl)-L-aspartate (PALA), an inhibitor of the synthesis of pyrimidine nucleotides, through amplification of cad, th...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.1.536
更新日期:1998-01-01 00:00:00
abstract::Cyclin B interacts with Cdc2 kinase to induce cell cycle events, particularly those of mitosis. The existence of cyclin B subtypes in several species has been known for some time, leading to speculation that key events of mitosis may be carried out by distinct functional classes of Cdc2/cyclin B. We report the discove...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.4.2286
更新日期:1993-04-01 00:00:00
abstract::The active beta-globin genes in chicken erythrocytes, like all active genes, reside in large chromatin domains which are preferentially sensitive to digestion by DNase I. We have recently proposed that the special structure of chromatin in active domains is maintained by torsional stress in the DNA (Villeponteau et al...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.5.1917
更新日期:1987-05-01 00:00:00
abstract::The glucose-activated transcription factor carbohydrate response element binding protein (ChREBP) induces the expression of hepatic glycolytic and lipogenic genes. The farnesoid X receptor (FXR) is a nuclear bile acid receptor controlling bile acid, lipid, and glucose homeostasis. FXR negatively regulates hepatic glyc...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01004-12
更新日期:2013-06-01 00:00:00
abstract::Human antigen R (ELAVL1; HuR) is perhaps the best-characterized RNA-binding protein. Through its overexpression in various tumor types, HuR promotes posttranscriptional regulation of target genes in multiple core signaling pathways associated with tumor progression. The role of HuR overexpression in pancreatic tumorig...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00427-17
更新日期:2018-01-16 00:00:00
abstract::Previous studies have shown that exposure of cells to high levels of replicational stress leads to permanent proliferation arrest that does not require p53. We have examined cellular responses to therapeutically relevant low levels of replicational stress that allow limited proliferation. Chronic exposure to low conce...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01316-06
更新日期:2007-08-01 00:00:00
abstract::Transcriptional coactivator with PDZ-binding motif (TAZ) physically interacts with a variety of transcription factors and modulates their activities involved in cell proliferation and mesenchymal stem cell differentiation. TAZ is highly expressed in the kidney, and a deficiency of this protein results in multiple rena...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00392-12
更新日期:2012-12-01 00:00:00
abstract::Eukaryotic splicing factors belonging to the SR family are essential splicing factors consisting of an N-terminal RNA-binding region and a C-terminal RS domain. They are believed to be involved in alternative splicing of numerous transcripts because their expression levels can influence splice site selection. We have ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.6.3116
更新日期:1997-06-01 00:00:00
abstract::Raf kinase inhibitory protein (RKIP/PEBP1), a member of the phosphatidylethanolamine binding protein family that possesses a conserved ligand-binding pocket, negatively regulates the mammalian mitogen-activated protein kinase (MAPK) signaling cascade. Mutation of a conserved site (P74L) within the pocket leads to a lo...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01271-08
更新日期:2009-03-01 00:00:00
abstract::Bone morphogenetic protein 7 (BMP7) stimulates renal branching morphogenesis via p38 mitogen-activated protein kinase (p38(MAPK)) and activating transcription factor 2 (ATF-2) (M. C. Hu, D. Wasserman, S. Hartwig, and N. D. Rosenblum, J. Biol. Chem. 279:12051-12059, 2004). Here, we demonstrate a novel role for integrin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.9.3648-3657.2005
更新日期:2005-05-01 00:00:00
abstract::When endoplasmic reticulum (ER) homeostasis is perturbed, an adaptive mechanism is triggered and named the unfolded protein response (UPR). Thus far, three known UPR signaling branches (IRE-1, PERK, and ATF-6) mediate the reestablishment of ER functions but can also lead to apoptosis if ER stress is not alleviated. Ho...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.02252-07
更新日期:2008-07-01 00:00:00
abstract::In the acellular slime mold Physarum polycephalum, the several hundred genes coding for rRNA are located on linear extrachromosomal DNA molecules of a discrete size, 60 kilobases. Each molecule contains two genes that are arranged in a palindromic fashion and separated by a central spacer region. We investigated how r...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.3.4.635
更新日期:1983-04-01 00:00:00
abstract::The androgen receptor (AR) is a nuclear hormone receptor superfamily member that conveys both trans repression and ligand-dependent trans-activation function. Activation of the AR by dihydrotestosterone (DHT) regulates diverse physiological functions including secondary sexual differentiation in the male and the induc...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.10.3373-3388.2002
更新日期:2002-05-01 00:00:00
abstract::The Mauriceville retroplasmid of Neurospora mitochondria encodes a novel reverse transcriptase that initiates cDNA synthesis de novo (i.e., without a primer) at the 3' CCA of the plasmid transcript's 3' tRNA-like structure (H. Wang and A. M. Lambowitz, Cell 75:1071-1081, 1993). Here, we show that the plasmid reverse t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.8.4526
更新日期:1997-08-01 00:00:00
abstract::The abundance of crystallins (> 80% of the soluble protein) in the ocular lens provides advantageous markers for selective gene expression during cellular differentiation. Here we show by functional and protein-DNA binding experiments that the chicken alpha A-crystallin gene is regulated by at least five control eleme...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.11.7363
更新日期:1994-11-01 00:00:00
abstract::To understand the mechanism of Axl signaling, we have initiated studies to delineate downstream components in interleukin-3-dependent 32D cells by using a chimeric receptor containing the recombinant epidermal growth factor (EGF) receptor extracellular and transmembrane domains and the Axl kinase domain (EAK [for EGF ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.1.135
更新日期:1996-01-01 00:00:00
abstract::Vascular smooth muscle cells (vSMCs) are key in the regulation of blood pressure and the engagement of vascular pathologies, such as hypertension, arterial remodeling, and neointima formation. The role of the Rac1 GTPase in these cells remains poorly characterized. To clarify this issue, we have utilized genetically e...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01066-14
更新日期:2014-12-01 00:00:00