Transcriptome Analysis in Prenatal IGF1-Deficient Mice Identifies Molecular Pathways and Target Genes Involved in Distal Lung Differentiation

Transcription factors Satb1 and Satb2 are involved in the processes of cortex development and maturation of neurons. Alterations in the expression of their target genes can lead to neurodegenerative processes. Molecular and cellular mechanisms of regulation of neurotransmission by these transcription factors remain poorly understood. In this study, we have shown that transcription factors Satb1 and Satb2 participate in the regulation of genes encoding the NMDA-, AMPA-, and KA- receptor subunits and the inhibitory GABA(A) receptor. Deletion of gene for either Satb1 or Satb2 homologous factors induces the expression of genes encoding the NMDA receptor subunits, thereby leading to higher amplitudes of Ca2+-signals in neurons derived from the Satb1-deficient (Satb1fl/+ * NexCre/+) and Satb1-null mice (Satb1fl/fl * NexCre/+) in response to the selective agonist reducing the EC50 for the NMDA receptor. Simultaneously, there is an increase in the expression of the Gria2 gene, encoding the AMPA receptor subunit, thus decreasing the Ca2+-signals of neurons in response to the treatment with a selective agonist (5-Fluorowillardiine (FW)). The Satb1 deletion increases the sensitivity of the KA receptor to the agonist (domoic acid), in the cortical neurons of the Satb1-deficient mice but decreases it in the Satb1-null mice. At the same time, the Satb2 deletion decreases Ca2+-signals and the sensitivity of the KA receptor to the agonist in neurons from the Satb1-null and the Satb1-deficient mice. The Satb1 deletion affects the development of the inhibitory system of neurotransmission resulting in the suppression of the neuron maturation process and switching the GABAergic responses from excitatory to inhibitory, while the Satb2 deletion has a similar effect only in the Satb1-null mice. We show that the Satb1 and Satb2 transcription factors are involved in the regulation of the transmission of excitatory signals and inhibition of the neuronal network in the cortical cell culture.

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Transcriptome Analysis Reveals a Promotion of Carotenoid Production by Copper Ions in Recombinant Saccharomyces cerevisiae

Microorganisms ◽

10.3390/microorganisms9020233 ◽

2021 ◽

Vol 9 (2) ◽

pp. 233

Author(s):

Buli Su ◽

Anzhang Li ◽

Ming-Rong Deng ◽

Honghui Zhu

Keyword(s):

Saccharomyces Cerevisiae ◽

Transcriptome Analysis ◽

Gene Expression Analysis ◽

Target Genes ◽

Copper Ions ◽

Carotenoid Production ◽

Carotenoid Accumulation ◽

Nutritional Components ◽

Differential Gene ◽

First Time

We previously constructed a Saccharomyces cerevisiae carotenoid producer BL03-D-4 which produced much more carotenoid in YPM (modified YPD) media than YPD media. In this study, the impacts of nutritional components on carotenoid accumulation of BL03-D-4 were investigated. When using YPM media, the carotenoid yield was increased 10-fold compared to using the YPD media. To elucidate the hidden mechanism, a transcriptome analysis was performed and showed that 464 genes changed significantly in YPM media. Furthermore, inspired by the differential gene expression analysis which indicated that ADY2, HES1, and CUP1 showed the most remarkable changes, we found that the improvement of carotenoid accumulation in YPM media was mainly due to the copper ions, since supplementation of 0.08 mM CuSO4 in YPD media could increase carotenoid yield 9.2-fold. Reverse engineering of target genes was performed and carotenoid yield could be increased 6.4-fold in YPD media through overexpression of ACE1. The present study revealed for the first time the prominent promotion of carotenoid yield by copper ions in engineered S. cerevisiae and provided a new target ACE1 for genetic engineering of S. cerevisiae for the bioproduction of carotenoids.

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KDM2B in polycomb repressive complex 1.1 functions as a tumor suppressor in the initiation of T-cell leukemogenesis

Blood Advances ◽

10.1182/bloodadvances.2018028522 ◽

2019 ◽

Vol 3 (17) ◽

pp. 2537-2549 ◽

Cited By ~ 6

Author(s):

Yusuke Isshiki ◽

Yaeko Nakajima-Takagi ◽

Motohiko Oshima ◽

Kazumasa Aoyama ◽

Mohamed Rizk ◽

...

Keyword(s):

T Cell ◽

Tumor Suppressor ◽

Zinc Finger ◽

Target Genes ◽

Lymphoblastic Leukemia ◽

Dependent Manner ◽

Polycomb Repressive Complex ◽

Human T Cell ◽

T Cell Leukemogenesis ◽

Deficient Mice

Abstract KDM2B together with RING1B, PCGF1, and BCOR or BCORL1 comprise polycomb repressive complex 1.1 (PRC1.1), a noncanonical PRC1 that catalyzes H2AK119ub1. It binds to nonmethylated CpG islands through its zinc finger-CxxC DNA binding domain and recruits the complex to target gene loci. Recent studies identified the loss of function mutations in the PRC1.1 gene, BCOR and BCORL1 in human T-cell acute lymphoblastic leukemia (T-ALL). We previously reported that Bcor insufficiency induces T-ALL in mice, supporting a tumor suppressor role for BCOR. However, the function of BCOR responsible for tumor suppression, either its corepressor function for BCL6 or that as a component of PRC1.1, remains unclear. We herein examined mice specifically lacking the zinc finger-CxxC domain of KDM2B in hematopoietic cells. Similar to Bcor-deficient mice, Kdm2b-deficient mice developed lethal T-ALL mostly in a NOTCH1-dependent manner. A chromatin immunoprecipitation sequence analysis of thymocytes revealed the binding of KDM2B at promoter regions, at which BCOR and EZH2 colocalized. KDM2B target genes markedly overlapped with those of NOTCH1 in human T-ALL cells, suggesting that noncanonical PRC1.1 antagonizes NOTCH1-mediated gene activation. KDM2B target genes were expressed at higher levels than the others and were marked with high levels of H2AK119ub1 and H3K4me3, but low levels of H3K27me3, suggesting that KDM2B target genes are transcriptionally active or primed for activation. These results indicate that PRC1.1 plays a key role in restricting excessive transcriptional activation by active NOTCH1, thereby acting as a tumor suppressor in the initiation of T-cell leukemogenesis.

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Transcriptome Analysis for Notch3 Target Genes Identifies Grip2 as a Novel Regulator of Myogenic Response in the Cerebrovasculature

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.112.251736 ◽

2013 ◽

Vol 33 (1) ◽

pp. 76-86 ◽

Cited By ~ 15

Author(s):

Charles Fouillade ◽

Céline Baron-Menguy ◽

Valérie Domenga-Denier ◽

Christelle Thibault ◽

Kogo Takamiya ◽

...

Keyword(s):

Transcriptome Analysis ◽

Target Genes ◽

Myogenic Response

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The ALK-1/SMAD/ATOH8 axis attenuates hypoxic responses and protects against the development of pulmonary arterial hypertension

Science Signaling ◽

10.1126/scisignal.aay4430 ◽

2019 ◽

Vol 12 (607) ◽

pp. eaay4430 ◽

Cited By ~ 3

Author(s):

Masato Morikawa ◽

Yoshihide Mitani ◽

Katarina Holmborn ◽

Taichi Kato ◽

Daizo Koinuma ◽

...

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Target Genes ◽

Hypoxia Inducible Factor ◽

Vascular Diseases ◽

Bmp Signaling ◽

Morphogenetic Protein ◽

Pulmonary Arterial ◽

Direct Target ◽

Deficient Mice

Dysregulated bone morphogenetic protein (BMP) signaling in endothelial cells (ECs) is implicated in vascular diseases such as pulmonary arterial hypertension (PAH). Here, we showed that the transcription factor ATOH8 was a direct target of SMAD1/5 and was induced in a manner dependent on BMP but independent of Notch, another critical signaling pathway in ECs. In zebrafish and mice, inactivation of Atoh8 did not cause an arteriovenous malformation–like phenotype, which may arise because of dysregulated Notch signaling. In contrast, Atoh8-deficient mice exhibited a phenotype mimicking PAH, which included increased pulmonary arterial pressure and right ventricular hypertrophy. Moreover, ATOH8 expression was decreased in PAH patient lungs. We showed that in cells, ATOH8 interacted with hypoxia-inducible factor 2α (HIF-2α) and decreased its abundance, leading to reduced induction of HIF-2α target genes in response to hypoxia. Together, these findings suggest that the BMP receptor type II/ALK-1/SMAD/ATOH8 axis may attenuate hypoxic responses in ECs in the pulmonary circulation and may help prevent the development of PAH.

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Response of Staphylococcus aureus to Salicylate Challenge

Journal of Bacteriology ◽

10.1128/jb.01149-06 ◽

2006 ◽

Vol 189 (1) ◽

pp. 220-227 ◽

Cited By ~ 30

Author(s):

James T. Riordan ◽

Arunachalam Muthaiyan ◽

Wayne Van Voorhies ◽

Christopher T. Price ◽

James E. Graham ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antimicrobial Resistance ◽

Transcriptome Analysis ◽

Target Genes ◽

Efflux Pump ◽

Multidrug Efflux ◽

Multidrug Efflux Pump ◽

Antibiotic Target ◽

Unique Mechanism ◽

Formate Metabolism

ABSTRACT Growth of Staphylococcus aureus with the nonsteroidal anti-inflammatory salicylate reduces susceptibility of the organism to multiple antimicrobials. Transcriptome analysis revealed that growth of S. aureus with salicylate leads to the induction of genes involved with gluconate and formate metabolism and represses genes required for gluconeogenesis and glycolysis. In addition, salicylate induction upregulates two antibiotic target genes and downregulates a multidrug efflux pump gene repressor (mgrA) and sarR, which represses a gene (sarA) important for intrinsic antimicrobial resistance. We hypothesize that these salicylate-induced alterations jointly represent a unique mechanism that allows S. aureus to resist antimicrobial stress and toxicity.

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Mature erythrocyte membrane homeostasis is compromised by loss of the GATA1-FOG1 interaction

Blood ◽

10.1182/blood-2011-09-382473 ◽

2012 ◽

Vol 119 (11) ◽

pp. 2615-2623 ◽

Cited By ~ 17

Author(s):

Atsushi Hasegawa ◽

Ritsuko Shimizu ◽

Narla Mohandas ◽

Masayuki Yamamoto

Keyword(s):

Membrane Proteins ◽

Target Genes ◽

Membrane Skeleton ◽

Severe Thrombocytopenia ◽

Mature Erythrocyte ◽

Adult Mice ◽

Comparable Level ◽

Genes Encoding ◽

Substitution Mutations ◽

Deficient Mice

Abstract GATA1 plays essential roles in erythroid gene expression. The N-terminal finger of GATA1 (GATA1-Nf) is important for association with FOG1. Substitution mutations in GATA1-Nf, such as GATA1V205M that diminish the GATA1-FOG1 association, have been identified in human thrombocytopenia and anemia cases. A mouse model of human thrombocytopenia has been established using a transgenic complementation rescue approach; GATA1-deficient mice were successfully rescued from embryonic lethality by excess expression of GATA1V205G, but rescued adult mice suffered from severe thrombocytopenia. In this study, we examined GATA1-deficient mice rescued with GATA1V205G at a comparable level to endogenous GATA1. Mice rescued with this level of GATA1V205G rarely survive to adulthood. Rescued newborns suffered from severe anemia and jaundice accompanied with anisocytosis and spherocytosis. Expression of Slc4a1, Spna1, and Aqp1 genes (encoding the membrane proteins band-3, α-spectrin, and aquaporin-1, respectively) were strikingly diminished, whereas expression of other canonical GATA1-target genes, such as Alas2, were little affected. Lack of these membrane proteins provoked perturbation of membrane skeleton. Importantly, the red cells exhibited increased reactive oxygen species accumulation. These results thus demonstrate that the loss of the GATA1-FOG1 interaction causes a unique combination of membrane protein deficiency and disturbs the function of GATA1 in maintaining erythroid homeostasis.

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Transcriptome analysis of a barley breeding program examines gene expression diversity and reveals target genes for malting quality improvement

BMC Genomics ◽

10.1186/1471-2164-11-653 ◽

2010 ◽

Vol 11 (1) ◽

Cited By ~ 20

Author(s):

María Muñoz-Amatriaín ◽

Yanwen Xiong ◽

Mark R Schmitt ◽

Hatice Bilgic ◽

Allen D Budde ◽

...

Keyword(s):

Gene Expression ◽

Quality Improvement ◽

Transcriptome Analysis ◽

Target Genes ◽

Breeding Program ◽

Malting Quality ◽

Barley Breeding

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Regulatory T cell-mediated resolution of lung injury: identification of potential target genes via expression profiling

Physiological Genomics ◽

10.1152/physiolgenomics.00131.2009 ◽

2010 ◽

Vol 41 (2) ◽

pp. 109-119 ◽

Cited By ~ 17

Author(s):

Neil R. Aggarwal ◽

Franco R. D'Alessio ◽

Kenji Tsushima ◽

Venkataramana K. Sidhaye ◽

Christopher Cheadle ◽

...

Keyword(s):

Gene Expression ◽

Lung Injury ◽

Acute Phase ◽

Adoptive Transfer ◽

Target Genes ◽

Expression Studies ◽

Rag 1 ◽

Gene Expression Studies ◽

Gene Ontologies ◽

Deficient Mice

In animal models of acute lung injury (ALI), gene expression studies have focused on the acute phase of illness, with little emphasis on resolution. In this study, the acute phase of intratracheal lipopolysaccharide (IT LPS)-induced lung injury was similar in wild-type (WT) and recombinase-activating gene-1-deficient (Rag-1−/−) lymphocyte-deficient mice, but resolution was impaired and resolution-phase lung gene expression remained different from baseline only in Rag-1−/− mice. By focusing on groups of genes involved in similar biological processes (gene ontologies) pertinent to inflammation and the immune response, we identified 102 genes at days 4 and 10 after IT LPS with significantly different expression between WT and Rag-1−/− mice. After adoptive transfer of isolated CD4+CD25+Foxp3+ regulatory T cells (Tregs) to Rag-1−/− mice at the time of IT LPS, resolution was similar to that in WT mice. Of the 102 genes distinctly changed in either WT or Rag-1−/− mice from our 7 gene ontologies, 19 genes reverted from the Rag-1−/− to the WT pattern of expression after adoptive transfer of Tregs, implicating those 19 genes in Treg-mediated resolution of ALI.

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Mef2C Is a Lineage-Restricted Target Gene of Scl/Tal1 and Regulates Megakaryopoiesis and B-Cell Homeostasis

Blood ◽

10.1182/blood.v112.11.278.278 ◽

2008 ◽

Vol 112 (11) ◽

pp. 278-278

Author(s):

Katrin E Rhodes ◽

Christos Gekas ◽

Laurraine Gereige ◽

Hildur Helgadottir ◽

Roberto Ferrari ◽

...

Keyword(s):

Transcription Factor ◽

B Cell ◽

Muscle Development ◽

Target Genes ◽

Fetal Liver ◽

Premature Aging ◽

Bhlh Transcription Factor ◽

Functional Requirements ◽

B Lymphoid ◽

Deficient Mice

Abstract The bHLH transcription factor stem cell leukemia/T-cell acute leukemia gene (Scl/Tal1) is a master regulator for hematopoiesis, essential for hematopoietic specification and proper differentiation of the erythroid and megakaryocyte lineages. However, the critical downstream targets of Scl remain undefined. To identify Scl target genes in hematopoietic cells, we performed gene expression analysis on HOX11-immortalized Sclfl/fl fetal liver cell lines. Analysis of the top 50 downregulated genes revealed several genes related to hematopoiesis including erythroid and megakaryocyte development, vasculogenesis, as well as genes/unknown ESTs that have not been previously linked to blood development. One of the top downregulated genes was transcription factor myocyte enhancer factor 2C (Mef2C). Mef2C−/− embryos die at E9.5, the same time as Scl−/− embryos, and exhibit severe defects in cardiac and muscle development. Analysis of Mef2C−/− embryos showed that, Mef2C, in contrast to Scl, is not required for specification into primitive or definitive hematopoietic lineages. To bypass the embryonic lethality, we utilized a conditionally targeted Mef2Cfl/fl strain and crossed it with a hematopoietic cell-specific VavCre strain that deactivates Mef2C shortly after the emergence of HSCs. Interestingly, adult VavCre+Mef2Cfl/fl mice exhibited severe platelet defects highly reminiscent to those observed in Scl deficient mice. The platelet counts were reduced, while platelet size was increased and the platelet shape and granularity was altered. Furthermore, megakaryopoiesis was severely impaired in vitro. ChIP-on-chip analysis revealed that Mef2C is directly regulated by Scl in megakaryocytic cells, but not in erythroid cells. In addition, an Scl independent requirement for Mef2C in B-lymphoid homeostasis was observed in Mef2C-deficient mice, characterized as severe age-dependent reductions of specific B-cell progenitor populations reminiscent of premature aging. In summary, this work identifies Mef2C as an integral member of hematopoietic transcription factors with distinct upstream regulatory mechanisms and functional requirements in megakaryocyte and B-lymphoid lineages.

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