Gata-Independent Regulation of Red Cell Specific Gene Expression.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1736-1736
Author(s):  
Jenna L. Galloway ◽  
Rebecca A. Wingert ◽  
Christine Thisse ◽  
Bernard Thisse ◽  
Leonard I. Zon
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Regulation Of Gene Expression ◽  
Actin Binding ◽  
Specific Gene ◽  
Cellular Functions ◽  
Novel Genes ◽  
Independent Manner ◽  
Repeat Protein ◽  
Gata Factors

Abstract During vertebrate embryonic hematopoiesis, the first blood cells can be identified by expression of the transcription factor genes scl and GATA2, followed by expression of GATA1, a gene required for the erythroid lineage. A high-throughput in situ hybridization screen in zebrafish analyzed the expression pattern of 3700 clones from a hematopoietic cDNA library and discovered 24 genes with expression in the blood. Examination of gene expression in Biklf, GATA1, GATA2, and GATA1/GATA2-deficient animals revealed that most blood genes are dependent upon GATA factors for expression rather than the Krüppel-like transcription factor Biklf. Three novel genes, expressed specifically in erythroid precursors, did not require GATA factors for their expression, demonstrating that some blood genes are regulated in a GATA-independent manner. These three genes were kelch-repeat protein (kelch repeats have been implicated in diverse cellular functions from actin binding to sequestering transcriptions factors), kiaa0650, which contains an SMC-hinge domain, and testhymin, which has no known structural motifs. By using combinations of antisense morpholinos to the known hematopoietic genes biklf , GATA1, GATA2, and scl, we were able to examine the regulation of these novel genes in double and triple knock-down embryos. While expression of kelch-repeat protein was lost in the absence of GATA1 and Biklf, expression of testhymin and kiaa0650 was maintained in GATA1/GATA2/Biklf-deficient embryos, suggesting that these similarly expressed genes are differentially regulated. As with GATA1, kiaa0650 and kelch-repeat protein required Scl for their expression in the early hematopoietic mesoderm while testhymin did not. Furthermore, loss of Scl and GATA2 did not completely ablate testhymin expression, suggesting that this gene is induced by factors upstream or parallel to Scl and GATA2. Taken together, our zebrafish studies establish a regulation of gene expression by a developmental hierarchy of specific transcription factors that act in combination during blood cell maturation.

scholarly journals The Forkhead Transcription Factor Fkh2 Regulates the Cell Division Cycle of Schizosaccharomyces pombe

2004 ◽  
Vol 3 (4) ◽  
pp. 944-954 ◽  
Author(s):  
Richard Bulmer ◽  
Aline Pic-Taylor ◽  
Simon K. Whitehall ◽  
Kate A. Martin ◽  
Jonathan B. A. Millar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Transcription Factor ◽  
Cell Division ◽  
Schizosaccharomyces Pombe ◽  
Regulation Of Gene Expression ◽  
Cell Division Cycle ◽  
Specific Gene ◽  
Dependent Manner ◽  
Forkhead Transcription Factor

ABSTRACT In eukaryotes the regulation of gene expression plays a key role in controlling cell cycle progression. Here, we demonstrate that a forkhead transcription factor, Fkh2, regulates the periodic expression of cdc15 + and spo12 + in the M and G1 phases of the cell division cycle in the fission yeast Schizosaccharomyces pombe. We also show that Fkh2 is important for several cell cycle processes, including cell morphology and cell separation, nuclear structure and migration, and mitotic spindle function. We find that the expression of fkh2 + is itself regulated in a cell cycle-dependent manner in G1 coincident with the expression of cdc18 +, a Cdc10-regulated gene. However, fkh2 + expression is independent of Cdc10 function. Fkh2 was found to be phosphorylated during the cell division cycle, with a timing that suggests that this posttranslational modification is important for cdc15 + and spo12 + expression. Related forkhead proteins regulate G2 and M phase-specific gene expression in the evolutionarily distant Saccharomyces cerevisiae, suggesting that these proteins play conserved roles in regulating cell cycle processes in eukaryotes.

scholarly journals ARID2 Chromatin Remodeler in Hepatocellular Carcinoma

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2152
Author(s):  
Robin Loesch ◽  
Linda Chenane ◽  
Sabine Colnot
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Associated Factors ◽  
Regulation Of Gene Expression ◽  
Specific Gene ◽  
Chromatin Remodeler ◽  
Chromatin Remodelers ◽  
Genes Encoding ◽  
Gene Alterations

Chromatin remodelers are found highly mutated in cancer including hepatocellular carcinoma. These mutations frequently occur in ARID (AT-rich Interactive Domain) genes, encoding subunits of the ATP-dependent SWI/SNF remodelers. The increasingly prevalent complexity that surrounds the functions and specificities of the highly modular BAF (BG1/BRM-associated factors) and PBAF (polybromo-associated BAF) complexes, including ARID1A/B or ARID2, is baffling. The involvement of the SWI/SNF complexes in diverse tissues and processes, and especially in the regulation of gene expression, multiplies the specific outcomes of specific gene alterations. A better understanding of the molecular consequences of specific mutations impairing chromatin remodelers is needed. In this review, we summarize what we know about the tumor-modulating properties of ARID2 in hepatocellular carcinoma.

scholarly journals Differential Regulation of Gene Expression of Alveolar Epithelial Cell Markers in Human Lung Adenocarcinoma-Derived A549 Clones

2015 ◽  
Vol 2015 ◽  
pp. 1-20 ◽  
Author(s):  
Hiroshi Kondo ◽  
Keiko Miyoshi ◽  
Shoji Sakiyama ◽  
Akira Tangoku ◽  
Takafumi Noma
Keyword(s):  
Gene Expression ◽  
Epithelial Cell ◽  
Mapk Pathway ◽  
Alveolar Epithelial Cell ◽  
Marker Gene ◽  
Regulation Of Gene Expression ◽  
Surfactant Protein ◽  
Specific Gene ◽  
Expression Levels ◽  
Alveolar Epithelial

Stem cell therapy appears to be promising for restoring damaged or irreparable lung tissue. However, establishing a simple and reproducible protocol for preparing lung progenitor populations is difficult because the molecular basis for alveolar epithelial cell differentiation is not fully understood. We investigated anin vitrosystem to analyze the regulatory mechanisms of alveolus-specific gene expression using a human alveolar epithelial type II (ATII) cell line, A549. After cloning A549 subpopulations, each clone was classified into five groups according to cell morphology and marker gene expression. Two clones (B7 and H12) were further analyzed. Under serum-free culture conditions,surfactant protein C(SPC), an ATII marker, was upregulated in both H12 and B7.Aquaporin 5(AQP5), an ATI marker, was upregulated in H12 and significantly induced in B7. When the RAS/MAPK pathway was inhibited,SPCandthyroid transcription factor-1(TTF-1) expression levels were enhanced. After treatment with dexamethasone (DEX), 8-bromoadenosine 3′5′-cyclic monophosphate (8-Br-cAMP), 3-isobutyl-1-methylxanthine (IBMX), and keratinocyte growth factor (KGF),surfactant protein BandTTF-1expression levels were enhanced. We found that A549-derived clones have plasticity in gene expression of alveolar epithelial differentiation markers and could be useful in studying ATII maintenance and differentiation.

Abstract 12905: Gene Expression and Expression Quantifying Trait Loci Analysis of Left Atrium of Patients With Post-operative Atrial Fibrillation

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Martin I Sigurdsson ◽  
Mahyar Heydarpour ◽  
Louis Saddic ◽  
Tzuu-Wang Chang ◽  
Stanton K Shernan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Atrial Fibrillation ◽  
Left Atrium ◽  
High Throughput ◽  
Specific Gene ◽  
Eqtl Analysis ◽  
Gene Variants ◽  
Nucleotide Polymorphisms ◽  
Novel Genes ◽  
Trait Loci

Introduction: The majority of information on the genetic background of atrial fibrillation (AF) results from genomic DNA variant analysis without consideration of tissue expression. Hypothesis: Analysis of tissue-specific gene expression in left atrium (LA) can further understanding of the molecular mechanism of identified AF risk variants, and identify novel genes and gene variants associated with AF. Methods: We isolated mRNA from samples of the LA free wall taken during mitral valve surgery in 62 Caucasian individuals. Gene expression in the LA was compared between patients who did and did not have post-operative AF (poAF) using high-throughput RNA expression. Using genotypes of 1.4 million single nucleotide polymorphisms (SNP) we performed cis expression quantifying trait loci (eQTL) analysis, correlating gene expression of each gene with the genotypes of adjacent (<1Mbp) SNPs. Results: We identified 23 differentially expressed genes in the LA of patients with poAF, including three potassium channel genes (KCNA7, KCNH8 and KCNK17). The largest expression difference was in LOC645323, a long non-coding RNA. The expression of PITX2, ZFHX3 and KCNN3, previously shown to be associated with AF, did not differ between patients with and without poAF. We identified 12,476 cis eQTL relationships in the LA, several of those included genetic regions and genes previously associated with AF. We confirmed an eQTL relationship between rs3744029 genotype and the expression of MYOZ1. Furthermore we describe a novel eQTL relationship between rs6795970 genotype and the expression of the SCN10A gene. Conclusions: We have analysed the human LA expression via high-throughput RNA sequencing, and identified novel genes and gene variants likely involved in the molecular pathophysiology of AF.

scholarly journals Minireview: Transcriptional Regulation in Development of Bone

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1012-1017 ◽  
Author(s):  
Tatsuya Kobayashi ◽  
Henry Kronenberg
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Bone Cells ◽  
Genetic Manipulation ◽  
Bone Development ◽  
Regulation Of Gene Expression ◽  
Bone Cell ◽  
Cellular Functions ◽  
Multiple Differentiation

Regulation of gene expression by transcription factors is one of the major mechanisms for controlling cellular functions. Recent advances in genetic manipulation of model animals has allowed the study of the roles of various genes and their products in physiological settings and has demonstrated the importance of specific transcription factors in bone development. Three lineages of bone cells, chondrocytes, osteoblasts, and osteoclasts, develop and differentiate according to their distinct developmental programs. These cells go through multiple differentiation stages, which are often regulated by specific transcription factors. In this minireview, we will discuss selected transcription factors that have been demonstrated to critically affect bone cell development. Further study of these molecules will lead to deeper understanding in mechanisms that govern development of bone.

scholarly journals Inducible cell-specific mouse models for paired epigenetic and transcriptomic studies of microglia and astroglia

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Ana J. Chucair-Elliott ◽  
Sarah R. Ocañas ◽  
David R. Stanford ◽  
Victor A. Ansere ◽  
Kyla B. Buettner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Affinity Purification ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Tissue Level ◽  
Cell Phenotype ◽  
Specific Gene ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific

AbstractEpigenetic regulation of gene expression occurs in a cell type-specific manner. Current cell-type specific neuroepigenetic studies rely on cell sorting methods that can alter cell phenotype and introduce potential confounds. Here we demonstrate and validate a Nuclear Tagging and Translating Ribosome Affinity Purification (NuTRAP) approach for temporally controlled labeling and isolation of ribosomes and nuclei, and thus RNA and DNA, from specific central nervous system cell types. Analysis of gene expression and DNA modifications in astrocytes or microglia from the same animal demonstrates differential usage of DNA methylation and hydroxymethylation in CpG and non-CpG contexts that corresponds to cell type-specific gene expression. Application of this approach in LPS treated mice uncovers microglia-specific transcriptome and epigenome changes in inflammatory pathways that cannot be detected with tissue-level analysis. The NuTRAP model and the validation approaches presented can be applied to any brain cell type for which a cell type-specific cre is available.

scholarly journals Cohesin-dependent regulation of gene expression during differentiation is lost in cohesin-mutated myeloid malignancies

Blood ◽  
2019 ◽  
Vol 134 (24) ◽  
pp. 2195-2208 ◽  
Author(s):  
Daniel Sasca ◽  
Haiyang Yun ◽  
George Giotopoulos ◽  
Jakub Szybinski ◽  
Theo Evan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Potential Role ◽  
Regulation Of Gene Expression ◽  
Specific Gene ◽  
Myeloid Malignancy ◽  
Erythroid Maturation ◽  
Acute Myeloid

Cohesin mutations are common in myeloid malignancy. Sasca et al elucidate the potential role of cohesin loss in myelodysplastic syndrome and acute myeloid leukemia (MDS/AML). They demonstrate that cohesin binding is critical for erythroid-specific gene expression and that reduction in cohesin impairs terminal erythroid maturation and promotes myeloid malignancy.

FOXA1 in breast cancer

2009 ◽  
Vol 11 ◽  
Author(s):  
Harikrishna Nakshatri ◽  
Sunil Badve
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Transcription Factor ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Gene Expression Signature ◽  
Specific Gene ◽  
Breast Cancers ◽  
Transcription Factor Network ◽  
Histopathological Classification

Breast cancer is a heterogeneous disease and classification is important for clinical management. At least five subtypes can be identified based on unique gene expression patterns; this subtype classification is distinct from the histopathological classification. The transcription factor network(s) required for the specific gene expression signature in each of these subtypes is currently being elucidated. The transcription factor network composed of the oestrogen (estrogen) receptor α (ERα), FOXA1 and GATA3 may control the gene expression pattern in luminal subtype A breast cancers. Breast cancers that are dependent on this network correspond to well-differentiated and hormone-therapy-responsive tumours with good prognosis. In this review, we discuss the interplay between these transcription factors with a particular emphasis on FOXA1 structure and function, and its ability to control ERα function. Additionally, we discuss modulators of FOXA1 function, ERα–FOXA1–GATA3 downstream targets, and potential therapeutic agents that may increase differentiation through FOXA1.

Chromatin-Modifying Enzymes in T Cell Development

2020 ◽  
Vol 38 (1) ◽  
pp. 397-419
Author(s):  
Michael J. Shapiro ◽  
Virginia Smith Shapiro
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Biological Effects ◽  
Critical Role ◽  
T Cell Development ◽  
Regulation Of Gene Expression ◽  
Chromatin Accessibility ◽  
Cell Development ◽  
Specific Gene ◽  
Dynamic Regulation

T cell development involves stepwise progression through defined stages that give rise to multiple T cell subtypes, and this is accompanied by the establishment of stage-specific gene expression. Changes in chromatin accessibility and chromatin modifications accompany changes in gene expression during T cell development. Chromatin-modifying enzymes that add or reverse covalent modifications to DNA and histones have a critical role in the dynamic regulation of gene expression throughout T cell development. As each chromatin-modifying enzyme has multiple family members that are typically all coexpressed during T cell development, their function is sometimes revealed only when two related enzymes are concurrently deleted. This work has also revealed that the biological effects of these enzymes often involve regulation of a limited set of targets. The growing diversity in the types and sites of modification, as well as the potential for a single enzyme to catalyze multiple modifications, is also highlighted.

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