Molecular mechanisms underlying the expression of the human HOX-5.1 gene

Cianetti, L; Cristofaro, Anna Di; Zappavigna, Vincenzo; Bottero, Lisa; Boccoli, Giovanni; Testa, Ugo; Russo, Giovanni; Boncinelli, Edoardo; Peschle, Cesare

doi:10.1093/nar/18.15.4361

Cited by 48 publications

(23 citation statements)

References 38 publications

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“…Nevertheless, it is quite clear that a large subset of them share some unusual features. They are often multiple, sometimes close together, sometimes spaced up to several kilobases apart (7,8,33). A relatively high proportion contain minimal promoters that do not have TATA boxes but have initiators instead.…”

Section: Discussionmentioning

confidence: 99%

Multiple positive and negative regulatory elements in the promoter of the mouse homeobox gene Hoxb-4.

1994

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Mouse Hoxb-4 (Hox-2.6) is a homeobox gene that belongs to a family which also includes Hoxa-4, Hoxc-4, and Hoxd-4 and that is related to the Deformed gene in Drosophila melanogaster. We have determined the sequence of 1.2 kb of 5' flanking DNA of mouse Hoxb-4 and by nuclease S1 and primer extension experiments identified two transcription start sites, P1 and P2, 285 and 207 nucleotides upstream of the ATG initiator codon, respectively. We have shown that this region harbors two independent promoters which drive CAT expression in several different cell lines with various efficiencies, suggesting that they are subject to cell-type-specific regulation. Through detailed mutational analysis, we have identified several cis-regulatory elements, located upstream and downstream of the transcription start sites. They include two cell-type-specific negative regulatory elements, which are more active in F9 embryonal carcinoma cells than in neuroblastoma cells (regions a and d at -226 to -186 and +169 to +205, respectively). An additional negative regulatory element has been delimited (region b between +22 and +113). Positive regulation is achieved by binding of HoxTF, a previously unknown factor, to the sequence GCCATTGG (+148 to + 155) that is essential for efficient Hoxb-4 expression. We have also defined the minimal promoter sequences and found that they include two 12-bp initiator elements centered around each transcription start site. The complex architecture of the Hoxb-4 promoter provides the framework for fine-tuned transcriptional regulation during embryonic development.Homeobox genes encode a large family of transcription factors and are found in a wide range of species, both invertebrate and vertebrate (reviewed in references 12, 17, and 23). In Drosophila melanogaster, the genes of theAntennapedia/ Ultrabithorax complexes, which are clustered together, specify the phenotypes of individual segments along the anteroposterior axis of the body. In mammals, there are four clusters of Antennapedia-class homeobox genes, called Hox genes, each on a different chromosome, which are presumed to have arisen by duplication and expansion of an ancestral complex. The genes in each of the four clusters that derive from the same ancestral gene are called paralogs. One-of the most remarkable features of both the invertebrate and the vertebrate Hox clusters is that there is a direct relationship between the position of a gene in the cluster and its expression domain. The genes at the 5' end, in the transcriptional sense, have the most posterior domains, and the genes at the 3' end have the most anterior.The role of Hox genes in mammalian development has been demonstrated by both ectopic expression (3,16,22,39) and by the introduction of loss-of-function mutations (5,6,18,21,27 shown that it is possible to recapitulate the normal expression pattern. In two cases, Hoxa-7 and Hoxb-4, multiple regulatory elements located downstream of the transcription start site are required (26, 38). However, these elements operate in opposite fashi...

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Section: Discussionmentioning

confidence: 99%

Multiple positive and negative regulatory elements in the promoter of the mouse homeobox gene Hoxb-4.

1994

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“…NTera-2 cells were maintained in their undifferentiated phenotype by continuous growth at high cell density (5-50 ϫ 10 6 cells/175 cm 2 flask), and differentiation was induced by seeding cells at 2 ϫ 10 6 cells per 175-cm 2 flasks in 10 Ϫ6 M retinoic acid (Sigma) as described (28). P19 cells were grown in ␣-modified minimal essential medium (Invitrogen) containing 7.5% heat-inactivated newborn calf serum (Invitrogen) and 2.5% fetal bovine serum (Invitrogen) and split 20 times every other day using 0.05% trypsin-0.02% EDTA as previously described (29).…”

Section: Methodsmentioning

confidence: 99%

The Interaction with HMG20a/b Proteins Suggests a Potential Role for β-Dystrobrevin in Neuronal Differentiation

Artegiani

Labbaye

Sferra

et al. 2010

Journal of Biological Chemistry

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␣ and ␤ dystrobrevins are cytoplasmic components of the dystrophin-associated protein complex that are thought to play a role as scaffold proteins in signal transduction and intracellular transport. In the search of new insights into the functions of ␤-dystrobrevin, the isoform restricted to non-muscle tissues, we performed a two-hybrid screen of a mouse cDNA library to look for interacting proteins. Among the positive clones, one encodes iBRAF/HMG20a, a high mobility group (HMG)-domain protein that activates REST (RE-1 silencing transcription factor)-responsive genes, playing a key role in the initiation of neuronal differentiation. We characterized the ␤-dystrobrevin-iBRAF interaction by in vitro and in vivo association assays, localized the binding region of one protein to the other, and assessed the kinetics of the interaction as one of high affinity. We also found that ␤-dystrobrevin directly binds to BRAF35/HMG20b, a close homologue of iBRAF and a member of a co-repressor complex required for the repression of neural specific genes in neuronal progenitors. In vitro assays indicated that ␤-dystrobrevin binds to RE-1 and represses the promoter activity of synapsin I, a REST-responsive gene that is a marker for neuronal differentiation. Altogether, our data demonstrate a direct interaction of ␤-dystrobrevin with the HMG20 proteins iBRAF and BRAF35 and suggest that ␤-dystrobrevin may be involved in regulating chromatin dynamics, possibly playing a role in neuronal differentiation.

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“…97,98,100 Several mechanisms have been identified that regulate expression of HOX genes. The identification of TAAT sequences and retinoic acid response elements in upstream regions allows the binding and activation or repression by homeoproteins [101][102][103][104][105][106] (autoregulation) and activation of expression by retinoic acid. [107][108][109][110][111][112][113][114][115][116] Early HOX gene expression in Drosophila is dependent on segmentation genes of the pairrule (activators) and gap (repressor) families.…”

Section: Hox Gene Expressionmentioning

confidence: 99%

The role of Homeobox genes in normal hematopoiesis and hematological malignancies

et al. 1999

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In the last decade it has become clear that homeobox containing genes (HOX genes) not only play a significant role in regulating body formation, but in addition, they are contributing to organization and regulation of hematopoiesis. Modern molecular technologies showed that deregulated expression or disruption of Hox genes can lead to altered characteristics of blood cells or disturbance of blood cell development. In this paper we review the role of HOX proteins in hematopoiesis and leukemogenesis and speculate about their possible target genes and involvement in lymphomagenesis.

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Molecular mechanisms underlying the expression of the human HOX-5.1 gene

Cited by 48 publications

References 38 publications

Multiple positive and negative regulatory elements in the promoter of the mouse homeobox gene Hoxb-4.

Multiple positive and negative regulatory elements in the promoter of the mouse homeobox gene Hoxb-4.

The Interaction with HMG20a/b Proteins Suggests a Potential Role for β-Dystrobrevin in Neuronal Differentiation

The role of Homeobox genes in normal hematopoiesis and hematological malignancies

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