• Title, Summary, Keyword: Hox

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The Existence of a Putative Regulatory Element in 3'-Untranslated Region of Proto-oncogene HOX11's mRNA

  • Li, Yue;Jiang, Zhao-Zhao;Chen, Hai-Xu;Leung, Wai-Keung;Sung, Joseph J.Y.;Ma, Wei-Jun
    • BMB Reports
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    • v.38 no.4
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    • pp.500-506
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    • 2005
  • HOX11 encodes a homeodomain-containing transcription factor which directs the development of the spleen during embryogenesis. While HOX11 expression is normally silenced through an unknown mechanism in all tissues by adulthood, the deregulation of HOX11 expression is associated with leukemia, such as T-cell acute lymphoblastic leukemia. The elucidation of regulatory elements contributing to the molecular mechanism underlying the regulation of HOX11 gene expression is of great importance. Previous reports of HOX11 regulatory elements mainly focused on the 5'-flanking region of HOX11 on the chromosome related to transcriptional control. To expand the search of putative cis-elements involved in HOX11 regulation at the post-transcriptional level, we analyzed HOX11 mRNA 3'-untranslated region (3'UTR) and found an AU-rich region. To characterize this AU-rich region, in vitro analysis of HOX11 mRNA 3'UTR was performed with human RNA-binding protein HuR, which interacts with AU-rich element (ARE) existing in the 3'UTR of many growth factors' and cytokines' mRNAs. Our results showed that the HOX11 mRNA 3'UTR can specifically bind with human HuR protein in vitro. This specific binding could be competed effectively by typical ARE containing RNA. After the deletion of the AU-rich region present in the HOX11 mRNA 3'UTR, the interaction of HOX11 mRNA 3'UTR with HuR protein was abolished. These findings suggest that HOX11 mRNA 3'UTR contains cis-acting element which shares similarity in the action pattern with RE-HuR interactions and may involve in the post-transcriptional regulation of the HOX11 gene.

Comparison of Expression Profiles of HOX Gene Family in Human Embryonic Stem Cells and Selected Human Fetal Tissues

  • Hwang Jung-Hye;Kim Kye-Seong;Kim Byung-Ju;Kwon Hee-Sun;Lee Man-Ryoul;Park Moon-Il;Jang Se-Jin
    • Journal of Microbiology and Biotechnology
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    • v.16 no.4
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    • pp.556-561
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    • 2006
  • The HOX genes coding homeodomain proteins have been suggested as a candidate molecular switch that determines the fates of cells during embryonic development and patterning. It is believed that a set of differentiation-specific HOX genes enter into a turn-on state during tissue differentiation, in contrast to stem cell-specific HOX genes that enter into a turn-off state. However, comprehensive data of expression profiles of HOX genes in human embryonic stem cells (hESC) and differentiated embryonic tissues are not available. In this study, we investigated the expression patterns of all 39 HOX genes in hESC and human fetal tissues and analyzed the relationships between hESC and each tissue. Of the 39 genes, 18 HOX genes were expressed in stem cells, and diverse expression patterning was observed in human fetal tissues when compared with stem cells. These results indicate that HOX genes could be main targets for switching of stem cell differentiation into tissues.

A Phylogenetic Analysis for Hox Linked Gene Families of Vertebrates

  • Kim, Sun-Woo;Jung, Gi-La;Lee, Jae-Hyoun;Park, Ha-Young;Kim, Chang-Bae
    • Animal cells and systems
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    • v.12 no.4
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    • pp.261-267
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    • 2008
  • The human chromosomes 2, 7, 12 and 17 show genomic homology around Hox gene clusters, is taken as evidence that these paralogous gene families might have arisen from a ancestral chromosomal segment through genome duplication events. We have examined protein data from vertebrate and invertebrate genomes to analyze the phylogenetic history of multi-gene families with three or more of their representatives linked to human Hox clusters. Topology comparison based upon statistical significance and information of chromosome location for these genes examined have revealed many of linked genes coduplicated with Hox gene clusters. Most linked genes to Hox clusters share the same evolutionary history and are duplicated in concert with each other. We conclude that gene families linked to Hox clusters may be suggestion of ancient genome duplications.

Hox Genes are Differentially Expressed during Mouse Placentation

  • Park, Sung-Joo;Lee, Ji-Yeon;Ma, Ji-Hyun;Kim, Helena Hye-Soo;Kim, Myoung-Hee
    • Biomedical Science Letters
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    • v.18 no.2
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    • pp.169-174
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    • 2012
  • The placenta is an extraembryonic tissue that is formed between mother and fetus and mediates delivery of nutrients and oxygen from the mother to the fetus. Because of its essential role in sustaining the growth of the fetus during gestation, defects in its development and function frequently result in fetal growth retardation or intrauterine death, depending on its severity. Vertebrate Hox genes are well known transcription factors that are essential for the proper organization of the body plan during embryogenesis. However, certain Hox genes have been known to be expressed in placenta, implying that Hox genes not only play a crucial role during embryonic patterning but also play an important role in placental development. So far, there has been no report that shows the expression pattern of the whole Hox genes during placentation. In this study, therefore, we investigated the Hox gene expression pattern in mouse placenta, from day 10.5 to 18.5 of gestation using real-time RT-PCR method. In general, the 5' posterior Hox genes were expressed more in the developing placenta compared to the 3' Hox genes. Statistical analysis revealed that the expression of 15 Hox genes (Hoxa9, -a11, -a13/ -b8, -b9/ -c6, -c9, -c13/ -d1, -d3, -d8, -d9, -d10, -d11, -d12) were significantly changed in the course of gestation. The majority of these genes showed highest expression at gestational day 10.5, suggesting their possible role in the early stage during placental development.

Increased HoxB4 Inhibits Apoptotic Cell Death in Pro-B Cells

  • Park, Sung-Won;Won, Kyung-Jong;Lee, Yong-Soo;Kim, Hye-Sun;Kim, Yu-Kyung;Lee, Hyeon-Woo;Kim, Bo-Kyung;Lee, Byeong-Han;Kim, Jin-Hoi;Kim, Dong-Ku
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.4
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    • pp.265-271
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    • 2012
  • HoxB4, a homeodomain-containing transcription factor, is involved in the expansion of hematopoietic stem cells and progenitor cells in vivo and in vitro, and plays a key role in regulating the balance between hematopoietic stem cell renewal and cell differentiation. However, the biological activity of HoxB4 in other cells has not been reported. In this study, we investigated the effect of overexpressed HoxB4 on cell survival under various conditions that induce death, using the Ba/F3 cell line. Analysis of phenotypical characteristics showed that HoxB4 overexpression in Ba/F3 cells reduced cell size, death, and proliferation rate. Moreover, the progression from early to late apoptotic stages was inhibited in Ba/F3 cells subjected to HoxB4 overexpression under removal of interleukin-3-mediated signal, leading to the induction of cell cycle arrest at the G2/M phase and attenuated cell death by Fas protein stimulation in vitro. Furthermore, apoptotic cell death induced by doxorubicin-treated G2/M phase cell-cycle arrest also decreased with HoxB4 overexpression in Ba/F3 cells. From these data, we suggest that HoxB4 may play an important role in the regulation of pro-B cell survival under various apoptotic death environments.

Effects of Dexamethasone on Embryo Development and Hox Gene Expression Patterns in Mice

  • Kim, Sang-Hoon;Lee, Ji-Yeon;Park, Sung-Joo;Kim, Myoung-Hee
    • Biomedical Science Letters
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    • v.17 no.3
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    • pp.231-238
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    • 2011
  • During pregnancy, stress induces maternal glucocorticoid secretion, which in turn is known to affect structural malformation, retardation of growth, reduced birth weight of the fetus. As Hox genes are master transcription factors which fulfill critical roles in embryonic development, we aimed to explore the possibility that alterations of the Hox gene expression might be involved in stress-induced malformation. The pregnant mice were injected with dexamethasone at a dose of 1 mg/kg or 10 mg/kg on day 7.5, 8.5 and 9.5 p.c. (post coitum), as well as saline as control. Embryos of E11.5 and E18.5 were obtained by sacrificing pregnant animals. Weight and crown-rump length (CRL) were measured. RT-PCR was performed to examine the Hox gene expression levels. Embryos given dexamethasone at day 7.5~9.5 p.c. had small CRL and weighed less both in E11.5 and E18.5. The percentage of embryos showing abnormalities was high in groups received high dose of dexamethasone. To define the molecular basis for abnormal embryonic development, we analyzed the Hox gene expression pattern and found that many Hox genes display altered expression. Effects of prenatal dexamethasone treatment on embryonic development might be associated with the aberrant Hox gene expression.

Post-transcriptional Regulation of Gcn5, a Putative Regulator of Hox in Mouse Embryonic Fibroblast Cells

  • Lee, You-Ra;Oh, Ji-Hoon;Kong, Kyoung-Ah;Kim, Myoung-Hee
    • Biomedical Science Letters
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    • v.18 no.2
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    • pp.165-168
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    • 2012
  • Hox proteins containing DNA-binding homedomain act as transcription factors important for anteroposterior body patterning during vertebrate embryogenesis. However, the precise mechanisms by which signal pathways are transduced to regulate the Hox gene expression are not clear. In the course of an attempt to isolate an upstream regulatory factor(s) controlling Hox genes, protein kinase B alpha (Akt1) has been identified as a putative regulator of Hox genes through in silico analysis (GEO profile). In the Gene Expression Omnibus (GEO) dataset GDS1784 at the NCBI (National Center for Biotechnology Information) site, Hox genes were differentially expressed depending on the presence or absence of Akt1. Since it was not well known how Akt1 regulates the specific Hox genes, whose transcription was reported to be regulated by epigenetic modifications such as histone acetylation, methylation etc., the expression of Gcn5, a histone acetyltransferase (HAT), was analyzed in wild type (WT) as well as in $Akt1^{-/-}$ mouse embryonic fibroblast (MEF) cells. RT-PCR analysis revealed that the amount of Gcn5 mRNA was similar in both WT and $Akt1^{-/-}$ MEFs. However, the protein level of Gcn5 was significantly increased in $Akt1^{-/-}$ MEF cells. The half life of Gcn5 was 1 hour in wild type whereas 8 hours in $Akt1^{-/-}$ MEF. These data all together, indicate that Gcn5 is post-transcriptionally down-regulated and the protein stability is negatively regulated by Akt1 in MEF cells.

A Study of Hox Gene Expression Profile During Murine Liver Regeneration

  • Boyeon-Youn;Kim, Byung-Gyu;Kim, Myoung-Hee
    • Biomedical Science Letters
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    • v.9 no.1
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    • pp.1-8
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    • 2003
  • Liver is an organ having an ability to regenerate by itself when it is damaged or removed. Since the research on the liver regeneration so far was regarding on the cellular multiplications not the formation of the shape, we intended to analyze the expression pattern of Hox genes during liver regeneration. RNA samples isolated from liver at the time of partial hepatectomy, 4 hours as well as 3 days later following regeneration were used to perform RT-PCR with Hox-specific degenerate primers. The PCR products were cloned, sequenced and analyzed through BLAST program. Genes belonging to the AbdB type Hox genes (paralogous groups IX-XIII) expressed predominantly during regeneration, while the other group (I-VII), especially Hoxal and bl seemed to be expressed continuously before and after regeneration. These data altogether imply that paralogous group IX and X genes including Hoxa10 and d10 seemed to be regeneration specific genes of liver.

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Synthetic Maternal Stress Hormone Can Modulate the Expression of Hox Genes

  • Yu, Sook-Jin;Lee, Ji-Yeon;Kim, Sang-Hoon;Deocaris, Custer C.;Kim, Myoung-Hee
    • Biomedical Science Letters
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    • v.15 no.3
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    • pp.249-255
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    • 2009
  • All living things have been developed efficient strategies to cope with external and internal environmental changes via a process termed 'homeostasis'. However, chronic prenatal maternal stress may significantly contributes to pregnancy complications by disturbing hypothalamic-pituitary-adrenal (HPA) axis and the automatic nervous system (ANS), and results in unfavorable development of the fetus. Dysregulation of these two major stress response systems lead to the increased secretion of the glucocorticoids (GCs) which are known to be essential for normal development and the maturation of the central nervous system. As Hox genes are master key regulators of the embryonic morphogenesis and cell differentiation, we aimed to determine the effects of dexamethasone, a potent synthetic glucocorticoid, on gene expression in mesenchymal stem cell C3H10T1/2. Analysis of 39 Hox genes based on reverse transcription PCR (RT-PCR) method revealed that the expression patterns of Hox genes were overall upregulated by long dexametasone treatment. These results indicate that maternal stress may have a deleterious effect on early developing embryo through the stress hormone, glucocorticoid.

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Isolation of labial Gene in the Oligochaeta Perionyx excavatus and Expression Patterns during Head Regeneration (지렁이 labial 유전자의 동정 및 머리재생 시 발현 양상에 관한 연구)

  • Cho Sung Jin;Lee Myung Sik;Tak Eun Sik;Hur So Young;Lee Jong Ae;Park Bum Joon;Cho Hyun Ju;Shin Chuog;Park Soon Cheol
    • The Korean Journal of Soil Zoology
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    • v.8 no.1_2
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    • pp.1-6
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    • 2003
  • Hox genes are pivotal in the control of morphogenesis along the anterior-posterior (AP) axis in various bilaterians. Several indications suggest their involvement in the control of cell growth and regeneration. For the labial full-length fragment, RACE-PCR was employed to obtain the 3' and 5' franking regions. Semi-quantitative RT-PCR analysis revealed that the labial expression began to increase at 12 hours after amputation. The peak expression was approximately 1.5-fold more than the unamputated controls. This result could give us information on the significance of Hox genes and the relationships between Hox genes during regeneration.

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