• 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.

• 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.

• 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.

• 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.

• Proceedings of the Zoological Society Korea Conference
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• 1995.10b
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• pp.241.2-241
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• 1995

No Abstract, See Full Text

• Journal of Life Science
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• v.25 no.6
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• pp.703-708
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• 2015

Hox genes encode a highly conserved family of homeodomain-containing transcription factors controlling vertebrate pattern formation along the anteroposterior body axis during embryogenesis. Retinoic acid (RA) is a key morphogen in embryogenesis and a critical regulator of both adult and embryonic cellular activity. Specifically, RA regulates Hox gene expression in mouse- or human-derived embryonic carcinoma (EC) cells. Histone modification has been reported to play a pivotal role in the process of RA-induced gene expression and cell differentiation. As histone modification is thought to play an essential role in RA-induced Hox gene expression, we examined RA-induced initiation of collinear expression of Hox genes and the corresponding histone modifications in F9 murine embryonic teratocarcinoma (EC) cells. Hox expression patterns and histone modifications were analyzed by semiquantitative RT-PCR, RNA-sequencing, and chromatin immuno-precipitation (ChIP)-PCR analyses. The Hoxc4 gene (D0) was initiated earlier than the Hoxc5 to –c10 genes (D3) upon RA treatment (day 0 [D0], day 1 [D1], and day 3 [D3]). The Hox nonexpressing D0 sample had a strong repressive marker, H3K27me3, than the D1 and D3 samples. In the D1 and D3 samples, reduced enrichment of the H3K27me3 marker was observed in the whole cluster. The active H3K4me3 marker was closely associated with the collinear expression of Hoxc genes. Thus, the Hoxc4 gene (D1) and all Hoxc genes (D3) expressed H3K4me3 upon transcription activation. In conclusion, these data indicated that removing H3K27me3 and acquiring H3K4me3 regulated RA-induced Hoxc gene collinearity in F9 cells.

• The Korean Journal of Soil Zoology
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• v.7 no.1_2
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• pp.29-34
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• 2002

Hox genes are a family of regulatory gene encoding transcription factor that primarily play a crucial role during development. Several indications suggest their involvement in the control of cell growth and regenration. RT-PCR and souther blot analysis revealed that labial-like gene was increasingly expressed along a spatial gradient in the anterior region of intact worm. During head and tail regeneration, labial-like gene was expressed only in the head region of regenerating body pieces, suggesting that the gene is involved in the anteroposterior patterning in earth-worm. This result could give us information on the significance of Hox genes and the relationship between Hox genes during regeneration.

• Korean Journal of Veterinary Research
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• v.35 no.1
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• pp.95-105
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• 1995

The human homolog of position specific element of mouse Hoxa-7 was studied using transgene. It contains a 1.1 kb human DNA (HCR)- a homolog to the intergenic region between Hoxa-7 and -9, which directs the position specific expression of Hoxa-7-, tk promoter, LacZ (${\beta}$-galactosidase) gene as a reporter, and polyadenylation signal of SV40 large T antigen. It was injected into the mice embryos, and the resulting transgenic embryos were analysed through PCR as well as genomic Southern blotting with placenta DNA. Out of 20 embryos analysed, two were transgenic. Among them, one transgenic embryo expressed transgene when stained with X-gal. The expression pattern was in analogy to that of the mouse Hoxa-7, showing spatially restricted expression pattern, Since the expression of ${\beta}$-galactosidase is regulated by the upstream human HCR sequence, it implies that the HCR is the plausible position specific regulatory element of human.

• BMB Reports
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• v.51 no.9
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• pp.450-455
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• 2018

Tamoxifen (TAM) is commonly used to treat estrogen receptor (ER)-positive breast cancer. Despite the remarkable benefits, resistance to TAM presents a serious therapeutic challenge. Since several HOX transcription factors have been proposed as strong candidates in the development of resistance to TAM therapy in breast cancer, we generated an in vitro model of acquired TAM resistance using ER-positive MCF7 breast cancer cells (MCF7-TAMR), and analyzed the expression pattern and epigenetic states of HOX genes. HOXB cluster genes were uniquely up-regulated in MCF7-TAMR cells. Survival analysis of in slico data showed the correlation of high expression of HOXB genes with poor response to TAM in ER-positive breast cancer patients treated with TAM. Gain- and loss-of-function experiments showed that the overexpression of multi HOXB genes in MCF7 renders cancer cells more resistant to TAM, whereas the knockdown restores TAM sensitivity. Furthermore, activation of HOXB genes in MCF7-TAMR was associated with histone modifications, particularly the gain of H3K9ac. These findings imply that the activation of HOXB genes mediate the development of TAM resistance, and represent a target for development of new strategies to prevent or reverse TAM resistance.

• Molecules and Cells
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• v.39 no.5
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• pp.395-402
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• 2016

Identifying Hoxc8 target genes is at the crux of understanding the Hoxc8-mediated regulatory networks underlying its roles during development. However, identification of these genes remains difficult due to intrinsic factors of Hoxc8, such as low DNA binding specificity, context-dependent regulation, and unknown cofactors. Therefore, as an alternative, the present study attempted to test whether the roles of Hoxc8 could be inferred by simply analyzing genes frequently coexpressed with Hoxc8, and whether these genes include putative target genes. Using archived gene expression datasets in which Hoxc8 was differentially expressed, we identified a total of 567 genes that were positively coexpressed with Hoxc8 in at least four out of eight datasets. Among these, 23 genes were coexpressed in six datasets. Gene sets associated with extracellular matrix and cell adhesion were most significantly enriched, followed by gene sets for skeletal system development, morphogenesis, cell motility, and transcriptional regulation. In particular, transcriptional regulators, including paralogs of Hoxc8, known Hox co-factors, and transcriptional remodeling factors were enriched. We randomly selected Adam19, Ptpn13, Prkd1, Tgfbi, and Aldh1a3, and validated their coexpression in mouse embryonic tissues and cell lines following $TGF-{\beta}2$ treatment or ectopic Hoxc8 expression. Except for Aldh1a3, all genes showed concordant expression with that of Hoxc8, suggesting that the coexpressed genes might include direct or indirect target genes. Collectively, we suggest that the coexpressed genes provide a resource for constructing Hoxc8-mediated regulatory networks.