Recently, many researches indicated the important role played by homeobox (HOX) gene family in normal hematopoiesis. As a kind of transcription factors, HOX gene products regulate and control the expression of target genes by binding to special DNA sequences. HOXB, a member of HOX gene family, especially HOXB(4), interests people greatly. It has been found that its expression relates closely to the self-renewal of hematopoietic stem cells and effective proliferation of hematopoietic progenitor cells. This review presents some new research progress in this area.
Animals ; Hematopoiesis ; genetics ; immunology ; physiology ; Hematopoietic Stem Cells ; cytology ; immunology ; metabolism ; Homeodomain Proteins ; genetics ; physiology ; Humans ; Multigene Family

Self-renewal and multilineage differentiation of hematopoietic stem cell (HSC) are their functional characteristics. The regulation of HSC self-renewal is governed by a balance between positive regulatory signals promoting growth and negative regulatory signals resulting in apoptosis. Among the positive regulatory signals, HOXB4 activates distinct pathways that enhance self-renewal divisions of HSC without overriding the regulatory mechanisms that maintain normal steady-state hemopoiesis. The upregulation of HOXB4 gene expression can greatly promote the HSC self-renewal, but does not affect the HSC differentiation, the morphology and function of linage-specific cells and terminally-differentiated blood cells. Furthermore, HOXB4 can enhance the hematopoietic potential of embryonic stem cell (ESC), promoting the differentiation of ESC into hematopoietic cells. As a consequence, upregulation of HOXB4 expression and/or corresponding HOXB4 target genes can have enormous therapeutical potential for human HSC in the stem cell transplantation and gene therapy. In this review the regulatory role of HOXB4 in HSC self-renewal, "zero" effect of HOXB4 on differentiation specificity of HSC lines and terminal differentiation cells, and molecular mechanisms of regulating HSC self-renewal by HOXB4 are summarised.
Animals ; Apoptosis ; genetics ; Cell Differentiation ; genetics ; Cell Proliferation ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; cytology ; metabolism ; Homeodomain Proteins ; genetics ; physiology ; Humans ; Transcription Factors ; genetics ; physiology

As a member of the hox gene family, hoxB4 gene encodes a class of DNA-dependent homeobox domain nucleoprotein, which is a specific transcription factor, playing an important role in regulating the balance between self-renewal and differentiation of hematopoietic stem cells (HSCs). Therefore, it is important to understand the mechanisms involved in regulating expression of hoxB4 in the HSC. Previous studies have suggested that some hoxB4 upstream regulatory factors, such as USF-1 (upstream activating factor -1), USF-2 (upstream activating factor -2) and NF-Y complex, as well as hematopoietic cytokines, such as platelet growth factor (TPO) and Wnt3a protein, play important regulatory roles in the expression of hoxB4 in hematopoietic stem cells. In this review the structure and biological characteristics of hoxB4, mechanisms involved in regulating expression of hoxB4 in the HSC are summarized.
CCAAT-Binding Factor ; metabolism ; Gene Expression Regulation ; Genes, Homeobox ; genetics ; physiology ; Hematopoietic Stem Cells ; metabolism ; Homeodomain Proteins ; genetics ; metabolism ; physiology ; Humans ; Transcription Factors ; genetics ; metabolism ; physiology ; Upstream Stimulatory Factors ; metabolism ; Wnt Proteins ; metabolism ; Wnt3 Protein ; Wnt3A Protein

Vernalization makes Arabidopsis and other cruciferous plants flowering earlier. During this process, an important plant homeodomain-finger(PHD-finger) protein named VIN3 is involved. The PHD domain was a conserved zinc-finger domain in eukaryotic organism. It used to take part in the interaction between proteins, especially the modification on histone of nucleosome, such as methylation, acetylation and phosphorylation. In vernaliazation pathway, the proteins translated by VERNALIZATION INSENSITIVE 3(VIN3) and homologous genes could result in methylation on H3K9 and H3K27 and deacetylation on H3K9 and H3K14 on chromatin histone of FLOWERING LOCUS C, a gene that inhibited flowering. The structure state of FLC would be changed from relaxation into compression. Then the transcription activity of FLC could be restrained and it couldn't inhibit flowering any more, so it would induce flowering earlier. This paper reviewed the function of PHD-finger proteins in vernalization pathway in Arabidopsis and other cruciferous plants, and overviewed the vernalization mechanism.
Amino Acid Sequence ; Arabidopsis ; genetics ; metabolism ; Arabidopsis Proteins ; genetics ; metabolism ; physiology ; Brassicaceae ; genetics ; DNA-Binding Proteins ; genetics ; metabolism ; physiology ; Gene Expression Regulation, Plant ; genetics ; physiology ; Histones ; metabolism ; Homeodomain Proteins ; genetics ; metabolism ; physiology ; MADS Domain Proteins ; genetics ; metabolism ; Molecular Sequence Data ; Transcription Factors ; genetics ; metabolism ; physiology ; Zinc Fingers

We investigated the microRNA172 (miR172)-mediated regulatory network for the perception of changes in external and endogenous signals to identify a universally applicable floral regulation system in ornamental plants, manipulation of which could be economically beneficial. Transgenic gloxinia plants, in which miR172 was either overexpressed or suppressed, were generated using Agrobacterium-mediated transformation. They were used to study the effect of altering the expression of this miRNA on time of flowering and to identify its mRNA target. Early or late flowering was observed in transgenic plants in which miR172 was overexpressed or suppressed, respectively. A full-length complementary DNA (cDNA) of gloxinia (Sinningia speciosa) APETALA2-like (SsAP2-like) was identified as a target of miR172. The altered expression levels of miR172 caused up- or down-regulation of SsAP2-like during flower development, which affected the time of flowering. Quantitative real-time reverse transcription PCR analysis of different gloxinia tissues revealed that the accumulation of SsAP2-like was negatively correlated with the expression of miR172a, whereas the expression pattern of miR172a was negatively correlated with that of miR156a. Our results suggest that transgenic manipulation of miR172 could be used as a universal strategy for regulating time of flowering in ornamental plants.
Arabidopsis/genetics* ; Arabidopsis Proteins/metabolism* ; Cloning, Molecular ; DNA, Complementary/metabolism* ; Flowers/physiology* ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Homeodomain Proteins/metabolism* ; Lamiales/physiology* ; MicroRNAs/metabolism* ; Nuclear Proteins/metabolism* ; Plants, Genetically Modified/physiology* ; Plasmids/metabolism* ; Polymerase Chain Reaction ; Transgenes

Alpha-Ketoglutarate-Dependent Dioxygenase FTO ; genetics ; Body Mass Index ; Body Weight ; genetics ; physiology ; Female ; Genotype ; Homeodomain Proteins ; genetics ; Humans ; Male ; Obesity ; genetics ; metabolism ; Transcription Factors ; genetics

OBJECTIVETo examine the transfection of Homeobox A13 (HOXA13) on epithelial-mesenchymal transition (EMT) and the expression of bone morphogenetic protein-7 (BMP-7) induced by albumin-overload in human kidney tubular epithelial cells (HKCs).

METHODSThe cultured HKCs were treated with 20 mg/mL human serum albumin (HSA) for 48 hours. Protein expression of cytokeratin (CK), vimentin and HOXA13 in the HKCs was assessed by Western blot. Protein expression of CK, vimentin, and BMP-7 was also detected in HKCs transfected with lipofectamine contained HOXA13 DNA.

RESULTSHSA induced EMT in HKCs, presented by decreased CK expression (P<0.01) and increased vimentin expression (P<0.01). The up-regulated expression of HOXA13 transfected by lipofectamine inhibited the level of EMT induced by HSA in HKCs (P<0.05). The decreased rate of BMP-7 protein expression induced by HSA was inhibited by over-expressed HOXA13 in HKCs (P<0.05).

CONCLUSIONSTransfection of HOXA13 in HKCs could inhibit the degree of EMT induced by albumin-overload, possibly by increasing BMP-7 expression.

Bone Morphogenetic Protein 7 ; genetics ; Cells, Cultured ; Epithelial Cells ; metabolism ; Epithelial-Mesenchymal Transition ; Homeodomain Proteins ; physiology ; Humans ; Keratins ; genetics ; Kidney Tubules ; metabolism ; Transfection ; Vimentin ; genetics

BACKGROUNDGastric cancer (GC) is one of the most prevalent malignancies in the world today, with a high mortality rate. CDX2 is a Drosophila caudal-related homeobox transcription factor that plays an important role in GC. Phosphatase and tensin homologue deleted from chromosome 10 (PTEN) is an important tumor suppressor which is widely expressed in normal human tissues. The aim of the study was to determine the relationship and mechanism between CDX2 and PTEN in invasion and migration of GC cells.

METHODSpcDNA3-CDX2 plasmids were transfected into MGC-803 cells to up-regulate CDX2 protein, and small interfering RNA-CDX2 was transfected to down-regulate CDX2. The influence of CDX2 or PTEN on cell migration and invasion was measured by invasion, migration and wound healing assays. Western blotting assay and immunofluorescence were used to detect the expression of CDX2, PTEN, phosphorylation of Akt, E-cadherin and N-cadherin. Statistical significance was determined by one-way analysis of variance.

RESULTSThe results showed that CDX2 reduced the migration and invasion of GC cells (P < 0.05), and inhibited the activity of Akt through down-regulating PTEN expression (P < 0.05). CDX2 also restrained epithelial-mesenchymal transition of GC cells.

CONCLUSIONSCDX2 inhibited invasion and migration of GC cells by PTEN/Akt signaling pathway, and that may be used for potential therapeutic target.

CDX2 Transcription Factor ; Cell Line, Tumor ; Cell Movement ; genetics ; physiology ; Chromosomes, Human, Pair 10 ; genetics ; Epithelial-Mesenchymal Transition ; genetics ; physiology ; Homeodomain Proteins ; genetics ; metabolism ; Humans ; Microfilament Proteins ; genetics ; metabolism ; PTEN Phosphohydrolase ; genetics ; Phosphoric Monoester Hydrolases ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Signal Transduction ; genetics ; physiology ; Stomach Neoplasms ; genetics ; metabolism ; pathology ; Tensins ; Wound Healing ; genetics ; physiology

Animals ; Apoptosis ; Cell Cycle ; Cell Cycle Proteins ; genetics ; metabolism ; physiology ; DNA Repair ; Homeodomain Proteins ; genetics ; metabolism ; physiology ; Humans ; Inhibitor of Growth Protein 1 ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; physiology ; Neoplasm Metastasis ; Neoplasms ; metabolism ; pathology ; Neovascularization, Pathologic ; pathology ; Nuclear Proteins ; genetics ; metabolism ; physiology ; Prognosis ; Receptors, Cytoplasmic and Nuclear ; genetics ; metabolism ; physiology ; Signal Transduction ; Transcription Factors ; genetics ; metabolism ; physiology ; Tumor Suppressor Protein p53 ; metabolism ; Tumor Suppressor Proteins ; chemistry ; genetics ; metabolism ; physiology

Low density lipoprotein receptor (LDLR) plays an important role in the cholesterol homeostasis. We examined the possible circadian regulation of LDLR and mechanism(s) underlying it. In mice, blood glucose and plasma triglyceride, total and high density lipoprotein cholesterol varied distinctively throughout a day. In addition, LDLR mRNA oscillated in the liver in a functional clock-dependent manner. Accordingly, analysis of human LDLR promoter sequence revealed three putative E-boxes, raising the possible regulation of LDLR expression by E-box-binding transcription factors. To test this possibility, human LDLR promoter reporter constructs were transfected into HepG2 cells and the effects of CLOCK/BMAL1, Hes1, and Hes6 expression were analyzed. It was found that positive circadian transcription factor complex CLOCK/BMAL1 upregulated human LDLR promoter activity in a serum-independent manner, while Hes family members Hes1 and Hes6 downregulated it only under serum-depleted conditions. Both effects were mapped to proximal promoter region of human LDLR, where mutation or deletion of well-known sterol regulatory element (SRE) abolished only the repressive effect of Hes1. Interestingly, hes6 and hes1 mRNA oscillated in an anti-phasic manner in the wild-type but not in the per1-/-per2-/- mouse. Comparative analysis of mouse, rat and human hes6 genes revealed that three E-boxes are conserved among three species. Transfection and site-directed mutagenesis studies with hes6 reporter constructs confirmed that the third E-box in the exon IV is functionally induced by CLOCK/BMAL1. Taken together, these results suggest that LDLR expression is under circadian control involving CLOCK/BMAL1 and Hes family members Hes1 and Hes6.
ARNTL Transcription Factors/physiology ; Animals ; Base Sequence ; Basic Helix-Loop-Helix Transcription Factors/*genetics/metabolism/physiology ; CLOCK Proteins/physiology ; Cholesterol/blood ; *Circadian Rhythm ; E-Box Elements ; Exons ; *Gene Expression Regulation ; Hep G2 Cells ; Homeodomain Proteins/*genetics/metabolism/physiology ; Homeostasis ; Humans ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; *Promoter Regions, Genetic ; Receptors, LDL/*genetics/metabolism ; Repressor Proteins/*genetics/metabolism/physiology ; Transcription, Genetic