Correction: Microarray Analyses of Glucocorticoid and Vitamin D3 Target Genes in Differentiating Cultured Human Podocytes

The biologically active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), modulates innate and adaptive immunity via genes regulated by the transcription factor vitamin D receptor (VDR). In order to identify the key vitamin D target genes involved in these processes, transcriptome-wide datasets were compared, which were obtained from a human monocytic cell line (THP-1) and peripheral blood mononuclear cells (PBMCs) treated in vitro by 1,25(OH)2D3, filtered using different approaches, as well as from PBMCs of individuals supplemented with a vitamin D3 bolus. The led to the genes ACVRL1, CAMP, CD14, CD93, CEBPB, FN1, MAPK13, NINJ1, LILRB4, LRRC25, SEMA6B, SRGN, THBD, THEMIS2 and TREM1. Public epigenome- and transcriptome-wide data from THP-1 cells were used to characterize these genes based on the level of their VDR-driven enhancers as well as the level of the dynamics of their mRNA production. Both types of datasets allowed the categorization of the vitamin D target genes into three groups according to their role in (i) acute response to infection, (ii) infection in general and (iii) autoimmunity. In conclusion, 15 genes were identified as major mediators of the action of vitamin D in innate and adaptive immunity and their individual functions are explained based on different gene regulatory scenarios.

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Identification of target genes in laryngeal squamous cell carcinoma by high-resolution copy number and gene expression microarray analyses

Oncogene ◽

10.1038/sj.onc.1209690 ◽

2006 ◽

Vol 25 (52) ◽

pp. 6997-7008 ◽

Cited By ~ 64

Author(s):

A-K Järvinen ◽

R Autio ◽

S Haapa-Paananen ◽

M Wolf ◽

M Saarela ◽

...

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

High Resolution ◽

Cell Carcinoma ◽

Copy Number ◽

Target Genes ◽

Laryngeal Squamous Cell Carcinoma ◽

Gene Expression Microarray ◽

Expression Microarray ◽

Microarray Analyses

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EZH2 Inhibitor DZNep Induces Apoptosis In Adult T-Cell Leukemia/Lymphoma Cells By BCL2 Suppression Via Regulation Of Mir-181a

Blood ◽

10.1182/blood.v122.21.4265.4265 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4265-4265 ◽

Cited By ~ 2

Author(s):

Sasaki Daisuke ◽

Hasegawa Hiroo ◽

Taniguchi Hiroaki ◽

Yoshitaka Imaizumi ◽

Uno Naoki ◽

...

Keyword(s):

T Cell ◽

Cell Lines ◽

Target Genes ◽

Expression Profiles ◽

Negative Regulator ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Adult T Cell Leukemia ◽

Microarray Analyses ◽

Bcl2 Expression

Abstract Background Adult T-cell leukemia/lymphoma (ATL) is a mature T-cell neoplasm originating from human T-cell leukemia virus type-1 (HTLV-1) infected cells. Its clinical behavior differs among patients and is sub-classified into 4 sub-types: smoldering and chronic as indolent subtypes, and acute and lymphoma as aggressive subtypes. Prognosis for patients with the aggressive subtypes is very poor with standard chemotherapy, thus a new therapeutic approach is urgently needed. Previously, we reported that EZH2, a part of the PRC2 complex, not only methylates histone, but also serves as a recruitment platform for DNA methyltransferases that methylate the promoter regions of target genes (tumor suppressor gene and miRNAs) and is overexpressed in ATL cells. We found that ATL cell lines were sensitive to DZNep (3-deazaneplanosin A), which has been shown to deplete EZH2 expression, and their proliferation was attenuated. In the present study, we clarified which target genes and miRNAs are involved in DZNep-induced ATL cell death. Results We performed microarray analyses using the ATL cell lines KK1, SO4, LMY1, and KOB to compare their gene expression profiles between cells treated and untreated with DZNep. The results showed that BCL2 transcripts in ATL cell lines were commonly suppressed by DZNep. In accordance with those findings, quantitative PCR analysis revealed that BCL2 transcripts were suppressed in DZNep-treated as compared to untreated ATL cell lines. We also confirmed that EZH2 and BCL2 protein expressions were clearly suppressed in the ATL cell lines by DZNep. These findings indicated that DZNep suppresses BCL2 expression at the transcriptional level in ATL cells. In addition, we performed another set of microarray analyses for miRNA expression profiles using primary ATL cells obtained from ATL patients and CD4 positive T-cells from healthy volunteers. The ATL cells showed decreased expression levels of several miRNAs, such as miR-101, miR-126, and miR-181a. Importantly, miR-181a has been shown to be regulated by EZH2, while miR-181a is a candidate negative regulator of BCL2 expression. Quantification of miR-181a transcripts to determine whether miR-181a is induced by DZNep showed that miR-181a was up-regulated in ATL cells by DZNep. These results strongly support the notion that miR-181a is suppressed by EZH2 and that BCL2 expression is regulated by miR-181a in ATL cells. Together, our findings indicate a unique apoptotic pathway of BCL2 suppression via miR181a and that the EZH2 inhibitor DZNep may become a novel therapeutic agent for ATL. Disclosures: No relevant conflicts of interest to declare.

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Different agonist- and antagonist-induced conformational changes in retinoic acid receptors analyzed by protease mapping.

Molecular and Cellular Biology ◽

10.1128/mcb.14.1.287 ◽

1994 ◽

Vol 14 (1) ◽

pp. 287-298 ◽

Cited By ~ 85

Author(s):

S Keidel ◽

P LeMotte ◽

C Apfel

Keyword(s):

Retinoic Acid ◽

Conformational Changes ◽

Vitamin D3 ◽

Target Genes ◽

Retinoic Acid Receptors ◽

Proteolytic Fragment ◽

Retinoid Receptors ◽

Agonist And Antagonist ◽

X Receptors ◽

Differentiation And Proliferation

The pleiotropic effects of retinoic acid on cell differentiation and proliferation are mediated by two subfamilies of nuclear receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). Recently the synthetic retinoid Ro 41-5253 was identified as a selective RAR alpha antagonist. As demonstrated by gel retardation assays, Ro 41-5253 and two related new RAR alpha antagonists do not influence RAR alpha/RXR alpha heterodimerization and DNA binding. In a limited trypsin digestion assay, complexation of RAR alpha with retinoic acid or several other agonistic retinoids altered the degradation of the receptor such that a 30-kDa proteolytic fragment became resistant to proteolysis. This suggests a ligand-induced conformational change, which may be necessary for the interaction of the DNA-bound RAR alpha/RXR alpha heterodimer with other transcription factors. Our results demonstrate that antagonists compete with agonists for binding to RAR alpha and may induce a different structural alteration, suggested by the tryptic resistance of a shorter 25-kDa protein fragment in the digestion assay. This RAR alpha conformation seems to allow RAR alpha/RXR alpha binding to DNA but not the subsequent transactivation of target genes. Protease mapping with C-terminally truncated receptors revealed that the proposed conformational changes mainly occur in the DE regions of RAR alpha. Complexation of RAR beta, RAR gamma, and RXR alpha, as well as the vitamin D3 receptor, with their natural ligands resulted in a similar resistance of fragments to proteolytic digestion. This could mean that ligand-induced conformational changes are a general feature in the hormonal activation of vitamin D3 and retinoid receptors.

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Microarray Analyses of SREBP-1 Target Genes

Understanding Lipid Metabolism with Microarrays and Other Omic Approaches ◽

10.1201/9781420030921-15 ◽

2004 ◽

pp. 261-272

Keyword(s):

Target Genes ◽

Microarray Analyses

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Identification of vitamin D3 target genes in human breast cancer tissue

The Journal of Steroid Biochemistry and Molecular Biology ◽

10.1016/j.jsbmb.2015.10.012 ◽

2016 ◽

Vol 164 ◽

pp. 90-97 ◽

Cited By ~ 12

Author(s):

Lei Sheng ◽

Paul H. Anderson ◽

Andrew G. Turner ◽

Kathleen I. Pishas ◽

Deepak J. Dhatrak ◽

...

Keyword(s):

Breast Cancer ◽

Vitamin D3 ◽

Human Breast Cancer ◽

Target Genes ◽

Breast Cancer Tissue ◽

Cancer Tissue ◽

Human Breast ◽

Human Breast Cancer Tissue

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Deacetylase Activity Is Required for Recruitment of the Basal Transcription Machinery and Transactivation by STAT5

Molecular and Cellular Biology ◽

10.1128/mcb.23.12.4162-4173.2003 ◽

2003 ◽

Vol 23 (12) ◽

pp. 4162-4173 ◽

Cited By ~ 103

Author(s):

Anne Rascle ◽

James A. Johnston ◽

Bruno Amati

Keyword(s):

Chromatin Remodeling ◽

Chromatin Immunoprecipitation ◽

Transcription Initiation ◽

Cellular Response ◽

Target Genes ◽

Trichostatin A ◽

Basal Transcription ◽

Basal Transcription Machinery ◽

Transcription Machinery ◽

Microarray Analyses

ABSTRACT The signal transducer and activator of transcription STAT5 plays a major role in the cellular response to cytokines, but the mechanism by which it activates transcription remains poorly understood. We show here that deacetylase inhibitors (trichostatin A, suberoylanilide hydroxamic acid, and sodium butyrate) prevent induction of endogenous STAT5 target genes, implying that a deacetylase activity is required for that process. Microarray analyses revealed that this requirement is common to all STAT5 target genes. Using chromatin immunoprecipitation, we show that, following STAT5 DNA binding, deacetylase inhibitors block transcription initiation by preventing recruitment of the basal transcription machinery. This inhibition is not due to effects on histone H3 and H4 acetylation or chromatin remodeling within the promoter region. This novel mechanism of transactivation by STAT5 provides a rationale for the use of deacetylase inhibitors for therapeutic intervention in STAT5-associated cancers.

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Primary vitamin D receptor target genes as biomarkers for the vitamin D3 status in the hematopoietic system

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2014.04.002 ◽

2014 ◽

Vol 25 (8) ◽

pp. 875-884 ◽

Cited By ~ 24

Author(s):

Julia Wilfinger ◽

Sabine Seuter ◽

Tomi-Pekka Tuomainen ◽

Jyrki K. Virtanen ◽

Sari Voutilainen ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Receptor ◽

Vitamin D3 ◽

Target Genes ◽

Hematopoietic System

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The transcriptome of the leukemogenic homeoprotein HOXA9 in human hematopoietic cells

Blood ◽

10.1182/blood-2003-07-2202 ◽

2004 ◽

Vol 103 (5) ◽

pp. 1676-1684 ◽

Cited By ~ 60

Author(s):

Sheri Tinnell Dorsam ◽

Christina M. Ferrell ◽

Glenn P. Dorsam ◽

Mika Kakefuda Derynck ◽

Ulka Vijapurkar ◽

...

Keyword(s):

Target Genes ◽

Expression Patterns ◽

Gene Families ◽

Lymphoid Cells ◽

Biologic Effects ◽

Human Acute Myeloid Leukemia ◽

Transient Overexpression ◽

High Level ◽

Microarray Analyses ◽

Hematopoietic Cell Lines

AbstractHematopoietic defects in HOXA9–/– mice demonstrate a key role for this homeoprotein in blood cell development. Conversely, enforced HOXA9 expression is leukemogenic in mice, and HOXA9 is frequently activated in human acute myeloid leukemia (AML). Although HOXA9 is thought to function as a transcription factor, few downstream targets have been identified. We searched for early HOXA9 target genes by using a transient overexpression strategy in 3 hematopoietic cell lines (2 myeloid, 1 lymphoid). cDNA microarray analyses identified 220 genes whose expression was modulated at least 2-fold. Expression signatures in myeloid and lymphoid cells demonstrated that HOXA9 functions as both an activator and repressor of a variety of genes in cell-specific patterns suggesting that the transcriptional effects of HOXA9 are largely dependent on the cell context. Transient transcription assays and target gene expression patterns in HOXA9–/– marrow cells imply that we have identified direct physiologic targets. Many target genes are expressed in CD34+ stem cells or are members of gene families involved in proliferation or myeloid differentiation. Expression of 14 HOXA9 target genes correlated with high-level HOXA9 expression in primary AML. These data suggest that many genes identified in this survey may mediate the biologic effects of HOXA9 in normal and leukemic hematopoiesis.

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