Gene Expression 15(1-2) Abstracts

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Volume 15, Number 2

Gene Expression, Vol. 15, pp. 51–59, 2011
1052-2166/10 $90.00 + .00
DOI: 10.3727/105221611X12973615737505
E-ISSN 1555-3884
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Reversible Epigenetic Modifications of the Two Cardiac Myosin Heavy Chain Genes During Changes in Expression

Kumar Pandya,* Benjamin Pulli,* Scott Bultman,† and Oliver Smithies*

*Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
†Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

The two genes of the cardiac myosin heavy chain (MHC) locus—alpha-MHC (aMHC) and beta-MHC (bMHC)—are reciprocally regulated in the mouse ventricle during development and in adult conditions such as hypothyroidism and pathological cardiac hypertrophy. Their expressions are under the control of thyroid hormone T3 levels. To gain insights into the epigenetic mechanisms that underlie this inducible and reversible switching of the aMHC and bMHC isoforms, we have investigated the histone modification patterns that occur over the two cardiac MHC promoters during T3-mediated reversible switching of gene expression. Mice fed a diet of propylthiouracil (PTU, an inhibitor of T3 synthesis) for 2 weeks dramatically reduce aMHC mRNA expression and increase bMHC mRNA levels to high levels, while a subsequent withdrawal of PTU diet for 2 weeks completely reverses the T3-mediated changes in MHC expression. Using hearts from mice treated in this way, we carried out chromatin immunoprecipitation-qPCR assays with antibodies against acetylated histone H3 (H3ac) and trimethylated histone (H3K4me3)—two well-documented markers of activation. Our results show that the reexpression of bMHC is associated at the bMHC promoter with increased H3ac but not H3K4me3. In contrast, the silencing of aMHC is associated at its promoter with decreased H3K4me3, but not decreased H3ac. The epigenetic changes at the two MHC promoters are completely reversed when the gene expression returns to initial levels. These data indicate that during reciprocal and inducible gene expression H3ac parallels bMHC isoform expression while H3K4me3 parallels expression of the tightly linked aMHC isoform.

Key words: Chromatin; Thyroid hormone; Heart; Histone; Acetylation; Methylation

Address correspondence to Oliver Smithies, D.Phil., Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, 701 Brinkhous Bullit Building, Chapel Hill, NC 27599-7525, USA. Tel: +1-919-966-6912; Fax: +1-919-966-8800; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 15, pp. 61–73, 2011
1052-2166/10 $90.00 + .00
DOI: 10.3727/105221611X12973615737541
E-ISSN 1555-3884
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Differential Allelic Distribution of V-ets Erythroblastosis Virus E26 Oncogene Homolog2 (ETS2) Functional Polymorphisms in Different Group of Patients

Arpita Chatterjee,* Samikshan Dutta,*1 Sanjit Mukherjee,† Nupur Mukherjee,‡ Sharmila Chandra,§ Ashis Mukherjee, Swagata Sinha,* Chinmay Kumar Panda,‡ Keya Chaudhuri,† and Kanchan Mukhopadyay*

*Manovikas Biomedical Research and Diagnostic Centre, MRIH, Kolkata, India
†Indian Institute of Chemical Biology, Kolkata, India
‡Chittaranjan National Cancer Institute, Kolkata, India
§Kothari Medical Centre and Research Institute, Kolkata, India
¶Netaji Subhash Chandra Bose Cancer Research Institute, Kolkata, India

V-ets erythroblastosis virus E26 oncogene homolog2 (ETS2), located at chromosome 21 and overexpressed in Down’s syndrome (DS), has known cancer regulatory functions. Because leukemia is of common occurrence in DS subjects while solid tumors are rare, we have explored the role of ETS2 functional genetic polymorphisms in this differential oncological development. In silico methods were used for identifying deleterious SNPs, tagged SNPs, and linkage disequilibrium followed by genotyping of 14 SNPs in Indo-Caucasoid individuals (N = 668). Significantly different allelic frequencies for rs457705, rs1051420, and rs1051425 were observed in Indian controls (N = 149) compared to other ethnic groups. A heterozygous “T” insertion, between chromosomal contig positions 40195541 and 40195542, was observed in DS subjects and their parents. rs461155 showed significant allelic and genotypic association in breast and oral cancer patients. Significantly higher occurrence of G-C haplotype (rs461155-rs1051425) was also observed in these patients compared to DS and leukemic patients. This is the first report on this type of allelic discrimination pattern of ETS2 under different disease conditions. From the data obtained it may be proposed that allelic discrimination of deleterious SNPs in ETS2 may play a regulatory role in the differential development of malignancy in DS subjects.

Key words: rs1051420; rs1051425; rs461155; rs457705; Acute lymphoblastic leukemia (ALL); Breast cancer; Down’s syndrome; Oral cancer

1Present address: Dongguk University, School of Medicine, Department of Anatomy, Gyeongju, South Korea.
Address correspondence to Kanchan Mukhopadhyay, Manovikas Biomedical Research and Diagnostic Centre, 482, Madudah, Plot I-24, Sec.-J, E.M. Bypass, Kolkata-700107, India. Tel: 91-033-4001-9179; Fax: 91-033-2442-8275; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 15, pp. 75–87, 2011
1052-2166/10 $90.00 + .00
DOI: 10.3727/105221611X12973615737587
E-ISSN 1555-3884
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

RNAi Silenced Dd-grp94 (Dictyostelium discoideum Glucose-Regulated Protein 94 kDa) Cell Lines in Dictyostelium Exhibit Marked Reduction in Growth Rate and Delay in Development

SANDHYA N. BAVISKAR* AND MALCOLM S. SHIELDS†

*Department of Biological Sciences, University of Arkansas-Fort Smith, Fort Smith, AR, USA
Department of Biological Sciences, Idaho State University, Pocatello, ID, USA

Glucose-regulated 94 kDa protein (Grp94) is a resident of the endoplasmic reticulum (ER) of multicellular eukaryotes. It is a constitutively expressed protein that is overexpressed in certain abnormal conditions of the cell such as depletion of glucose and calcium, and low oxygen and pH. The protein is also implicated in diseased conditions like cancer and Alzheimer’s disease. In this study, the consequences of downregulation of Grp94 were investigated at both unicellular and multicellular stages of Dictyostelium discoideum. Previous studies have shown the expression of Dd-Grp94 (Dictyostelium discoideum glucose-regulated 94 kDa protein) in wild-type cells varies during development, and overexpression of Dd-Grp94 leads to abnormal cell shape and inhibition of development (i.e., formation of fruiting bodies). Grp94 is a known calcium binding protein and an efficient calcium buffer. Therefore, in the present study we hypothesized that downregulation of Dd-Grp94 protein would affect Dictyostelium cell structure, growth, and development. We found that Dd-grp94 RNAi recombinants exhibited reduced growth rate, cell size, and a subtle change in cell motility compared to the parental cells. The recombinants also exhibited a delay in development and small fruiting bodies. These results establish that Ddgrp94 plays a crucial role in determining normal cell structure, growth and differentiation.

Key words: Dictyostelium discoideum glucose-regulated 94 kDa protein (Dd-Grp94); RNA interference; Glucose-regulated 94 kDa protein (Grp94); Endoplasmic reticulum

Address correspondence to Sandhya N. Baviskar, Department of Biological Sciences, University of Arkansas-Fort Smith, 5210 Grand Avenue, Fort Smith, AR 72913, USA. Tel: 479-788-7789; Fax: 479-788-7612; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 15, pp. 89–102, 2011
1052-2166/10 $90.00 + .00
DOI: 10.3727/105221611X12973615737622
E-ISSN 1555-3884
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Intronic DNA Elements Regulate Androgen-Dependent Expression of the Murine Nkx3.1 Gene

Chinatsu Kojima,* Yan Zhang,* and Warren E. Zimmer*†‡

*Department of Systems Biology and Translational Medicine, College of Medicine, Texas A&M Health Science Center, College Station, TX, USA
†Interdisciplinary Faculty of Toxicology, Texas A&M University System, College Station, TX, USA
‡Faculty of Genetics, Texas A&M University System, College Station, TX, USA

Nkx3.1
is a well-conserved homeobox gene that is involved in development, differentiation and maintenance of prostate epithelial cells. Nkx3.1 expression is induced by androgen in prostate epithelia and, as such, our interest is to understand the mechanism(s) for this androgen-dependent expression in normal epithelial cells. In this report, we show that the region of DNA sequence 2.7 kilobases in front of the mouse Nkx3.1 gene drives enhanced transcription in prostate epithelia cells; however, this segment was not capable of androgen-directed regulation. Among the multiple, potential androgen response elements (AREs) identified by scanning sequences near and within the gene, two sequences within the intron of the murine Nkx3.1 gene were demonstrated to confer androgen-dependent transcription in reporter gene transfection experiments. Each of the elements, termed ARE A and ARE B, contained a 6-base pair core sequence, TGTTCT, that has been described as an androgen receptor half-site binding sequence, separated by 498 base pairs of DNA. Both of the intronic half-sites bind activated androgen receptor from a variety of sources, albeit with different apparent affinities. This region of the Nkx3.1 gene demonstrates a high degree of conservation among diverse species and mutagenesis experiments demonstrated that both elements are required for androgen stimulation. Taken together, our study shows that androgen-dependent transcription of the mouse Nkx3.1 gene is conferred through a noncanonical element within the intron of the gene.

Key words: Nkx3.1; Androgen receptor; Steroid regulation; Prostate; Cancer; Epithelia; Androgen response element (ARE)

Address correspondence to Dr. Warren E. Zimmer, Room 310B Reynolds Medical Building, Department of Systems Biology and Translational Medicine, College of Medicine, Texas A&M Health Science Center, College Station, TX 77843-1114, USA. Tel: (979) 845-2896; Fax: (979) 862-4638; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

 

Volume 15, Number 1

Gene Expression, Vol. 15, pp. 1–11, 2010
1052-2166/10 $90.00 + .00
DOI: 10.3727/105221610X12819686555015
E-ISSN 1555-3884
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Review

ATF3, a Hub of the Cellular Adaptive-Response Network, in the Pathogenesis of Diseases: Is Modulation of Inflammation a Unifying Component?

Tsonwin Hai,*†‡ Christopher C. Wolford,*† and Yi-Seok Chang*†‡

*
Department of Molecular and Cellular Biochemistry, Ohio State University, Columbus, OH, USA
†Center for Molecular Neurobiology, Ohio State University, Columbus, OH, USA
‡Molecular, Cellular, and Developmental Biology Program, Ohio State University, Columbus, OH, USA

Activating transcription factor 3 (ATF3) gene encodes a member of the ATF family of transcription factors and is induced by various stress signals. All members of this family share the basic region-leucine zipper (bZip) DNA binding motif and bind to the consensus sequence TGACGTCA in vitro. Previous reviews and an Internet source have covered the following topics: the nomenclature of ATF proteins, the history of their discovery, the potential interplays between ATFs and other bZip proteins, ATF3-interacting proteins, ATF3 target genes, and the emerging roles of ATF3 in cancer and immunity (see footnote 1). In this review, we present evidence and clues that prompted us to put forth the idea that ATF3 functions as a “hub” of the cellular adaptive-response network. We will then focus on the roles of ATF3 in modulating inflammatory response. Inflammation is increasingly recognized to play an important role for the development of many diseases. Putting this in the context of the hub idea, we propose that modulation of inflammation by ATF3 is a unifying theme for the potential involvement of ATF3 in various diseases.

Key words: Activating transcription factor 3 (ATF3); Adaptive-response network; Inflammatory response

1For nomenclature, history, and interplay with other bZip proteins, see (21,22,24,25); for interacting proteins and target genes, see (48); for ATF3 in cancer and immunity, see (64).
Address correspondence to Tsonwin Hai, 174 Rightmire Hall, 1060 Carmack Road, Columbus, OH 43210, USA. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 15, pp. 13–25, 2010
1052-2166/10 $90.00 + .00
DOI: 10.3727/105221610X12819686555051
E-ISSN 1555-3884
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Review

Emerging Roles for XBP1, a sUPeR Transcription Factor

Yin He,* Shengyi Sun,† Haibo Sha,‡ Ziying Liu,† Liu Yang,† Zhen Xue,§ Hui Chen,‡ and Ling Qi*†‡§

*Graduate Program in Genetics and Development, Cornell University, Ithaca, NY, USA
†Graduate Program in Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY, USA
‡Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA
§Graduate Program in Nutrition, Cornell University, Ithaca, NY, USA

X-box binding protein 1 (XBP1) is a unique basic region leucine zipper (bZIP) transcription factor whose active form is generated by a nonconventional splicing reaction upon disruption of homeostasis in the endoplasmic reticulum (ER) and activation of the unfolded protein response (UPR). XBP1, first identified as a key regulator of major histocompatibility complex (MHC) class II gene expression in B cells, represents the most conserved signaling component of UPR and is critical for cell fate determination in response to ER stress. Here we review recent advances in our understanding of this multifaceted transcription factor in health and diseases.

Key words: X-box binding protein 1 (XBP1); Inositol-requiring enzyme 1 (IRE1á); Unfolded protein response (UPR); Splicing; Transcription; Diseases

Address correspondence to Ling Qi, Ph.D., 307 Biotech Building, Cornell University, Ithaca, NY 14853, USA. Tel: (607) 254-8857; Fax: (607) 255-6249; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 15, pp. 27–42, 2010
1052-2166/10 $90.00 + .00
DOI: 10.3727/105221610X12819686555097
E-ISSN 1555-3884
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Early Transcriptional Events During Osteogenic Differentiation of Human Bone Marrow Stromal Cells Induced by Lim Mineralization Protein 3

Camilla Bernardini,* Nathalie Saulnier,† Claudio Parrilla,‡ Enrico Pola,§ Andrea Gambotto,¶ Fabrizio Michetti,*# Paul D. Robbins,¶ and Wanda Lattanzi*

*Institute of Anatomy and Cell Biology, Catholic University, School of Medicine, Rome, Italy
†Department of Internal Medicine, Catholic University, School of Medicine, Rome, Italy
‡Department of Otolaryngology, Catholic University, School of Medicine, Rome, Italy
§Department of Orthopedics, Catholic University, School of Medicine, Rome, Italy
¶Department of Microbiology and Molecular Genetics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA
#
Latium Musculo-Skeletal Tissue Bank, Rome, Italy

Lim mineralization protein-3 (LMP3) induces osteoblast differentiation by regulating the expression and activity of certain molecules involved in the osteogenic cascade, including those belonging to the bone morphogenetic protein (BMP) family. The complete network of molecular events involved in LMP3-mediated osteogenesis is still unknown. The aim of this study was to analyze the genome-wide gene expression profiles in human mesenchyma stem cells (hMSC) induced by exogenous LMP3 to mediate osteogenesis. For this purpose hMSC were transduced with a defective adenoviral vector expressing the human LMP3 gene and microarray analysis was performed 1 day post-adenoviral transduction. Cells transduced with the vector backbone and untransduced cells were used as independent controls in the experiments. Microarray data were independently validated by means of real-time PCR on selected transcripts. The statistical analysis of microarray data produced a list of 263 significantly (p < 0.01) differentially expressed transcripts. The biological interpretation of the results indicated, among the most noteworthy effects, the modulation of genes involved in the TGF-β1 pathway: 88 genes coding for key regulators of the cell cycle regulatory machinery and 28 genes implicated in the regulation of cell proliferation along with the development of connective, muscular, and skeletal tissues. These results suggested that LMP3 could affect the fine balance between cell proliferation/differentiation of mesenchymal cells mostly by modulating the TGF-β1 signaling pathway.

Key words: Lim mineralization protein-3 (LMP3); Microarray; Osteogenesis; Mesechymal cells; Gene expression

Address correspondence to Wanda Lattanzi, M.D., Ph.D., Institute of Anatomy and Cell Biology, Catholic University, School of Medicine, Largo F. Vito, 1 00168 Rome, Italy. Tel: +39 06 30154915/4711; Fax: +39 06 30154813; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 15, pp. 43–50, 2010
1052-2166/10 $90.00 + .00
DOI: 10.3727/105221610X12819686555132
E-ISSN 1555-3884
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Domain Within the C Protein of Human Parainfluenza Virus Type 3 That Regulates Interferon Signaling

Hongxia Mao, Santanu Chattopadhyay, and Amiya K. Banerjee

Virology Section, Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

Human parainfluenza virus type 3 (HPIV3), one of the paramyxoviruses, uses its accessory C protein as an antagonist against interferon (IFN)-mediated host innate immunity. We have previously shown that the C protein significantly decreased the IFN-induced phosphorylation of signal transducer and activator of transcription (Stat) 1 and the formation of gamma IFN activation factor (GAF) complex, thus abrogating the antiviral activity of the IFNs against vesicular stomatitis virus (VSV) replication. Here, by mutational analyses we demonstrated that the N-terminal truncation of the C protein (CNΔ25 and CNΔ50) substantially (~50%) recovers the IFN-induced responses, suggesting the critical role of the N-terminal region of the C protein in IFN signaling. Furthermore, our results indicate that the charged amino acid residues within the N-terminal region of the C protein regulate the antagonistic effect of the C protein on IFN signaling.

Key words: Human parainfluenza virus type 3 (HPIV3); C protein; Interferon (IFN) antagonist

Address correspondence to Amiya K. Banerjee, NN1-06, Virology Section/Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Tel: (216) 444-0625; Fax: (216) 444-2998; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it