Human HOX genes are differentially activated by retinoic acid in embryonal carcinoma cells according to their position within the four loci

Stornaiuolo, Anna; Acampora, Dario; Pannese, Maria; D’Esposito, Maurizio; Morelli, Francesco; Migliaccio, Enrica; Rambaldi, M; Faiella, A.; Nigro, Vincenzo; Simeone, Antonio; Boncinelli, Edoardo

doi:10.1016/0922-3371(90)90015-o

Cited by 61 publications

(39 citation statements)

References 44 publications

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“…5). The deduced amino acid sequence of GHox-li is identical to the published sequence for human HOXlI (the 61 amino acids of the homeodomain plus the 5 amino acids immediately following the homeodomain) and differs from the equivalent regions of HOX4F and HOX3H (a paralog of HOX4F in the HOX 3 cluster) (Stornaiuolo et al, 1990) by 3 and 5 amino acids, respectively. One of the three GHox-li clones (pGHoxlic) contains 187 bp of sequence at its 5' end, which is different from the sequence in the other two clones ( Figs.…”

Section: Isolation and Characterization Of Ghox-li Andmentioning

confidence: 64%

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The pattern of expression of the chicken homolog of HOX1I in the developing limb suggests a possible role in the ectodermal inhibition of chondrogenesis

Rogina

Coelho

Kosher

et al. 1992

Developmental Dynamics

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Homeobox-containing genes have been implicated in a variety of patterning events during vertebrate limb development. In an attempt to isolate cDNAs corresponding to 5' members of the chicken HOX 4 cluster of homeobox-containing genes, a cDNA library constructed from mRNAs expressed during early stages of chick limb development was screened with probes generated by the polymerase chain reaction (PCR) using oligonucleotide primers corresponding to sequences in the homeoboxes of the human HOX4C and HOX4F genes, the human homologs of Hox-4.4 and Hox-4.6. This screening resulted in the isolation of full length cDNAs for the chicken homolog of HOX4F (cognate of mouse Hox-4.6), which we have termed GHox-4.6, and the chicken homolog of human HOXlI, which we have named GHox-li, a paralog of Hox-4.6 in the HOX 1 cluster. The homeodomains encoded by GHox-4.6 and GHox-li differ by only three amino acids, and the two proteins show extensive similarity along their entire lengths. Despite their sequence similarity, in situ hybridization analysis has revealed that GHox-4.6 and GHox-li exhibit strikingly different spatial patterns of expression during embryonic chick limb development. At early stages of limb development (stages 20-22), GHox-4.6 transcripts are present in high amounts throughout the posterior half of the limb mesoderm and are absent from the anterior half of the mesoderm, an expression pattern consistent with the possible involvement of GHox-4.6 in the specification of posterior positional identity. In contrast, GHox-li exhibits no distinct anterior-posterior polarity of expression at stage 22, but rather is expressed in high amounts throughout the mesenchyme of the limb bud. At later stages of development (stage 25), GHox-li continues to be expressed in high amounts throughout the undifferentiated mesenchyme subjacent to the apical ectodermal ridge, and, in addition, is expressed in the mesodermal cells in the proximal peripheral regions of the limb bud subjacent to the ectoderm which are differentiating into nonchondrogenic lineages. bud where chondrogenic differentiation is occurring. Thus, GHox-li is expressed by the undifferentiated subridge mesenchymal cells and proximal peripheral mesenchymal cells of the limb bud that are being inhibited from undergoing chondrogenesis by the apical ectodermal ridge and nonridge ectoderm. These observations suggest the possibility that GHox-li may be involved in mediating the antichondrogenic effect of limb ectoderm, and that the cessation of GHox-li expression may be required for chondrogenic differentiation to occur in the proximal central core of the limb bud.

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Section: Isolation and Characterization Of Ghox-li Andmentioning

confidence: 64%

“…The proteins encoded by these two paralogous genes differ by only three amino acids in their home- Acampora et al (1989), and the HOX3H sequence is from Stornaiuolo et al (1990).…”

Section: Isolation and Characterization Of Ghox-li Andmentioning

confidence: 99%

The pattern of expression of the chicken homolog of HOX1I in the developing limb suggests a possible role in the ectodermal inhibition of chondrogenesis

Rogina

Coelho

Kosher

et al. 1992

Developmental Dynamics

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“…Systematic analysis of all four clusters showed that none of the 38 HOX genes is expressed in EC stem cells at levels detectable by Northern analysis, whereas 24 HOX genes are activated after 7 days of induction with 10 pM RA. Expression of 14 HOX genes, all belonging to the most 5' paralogous groups, remains undetectable even after longer exposure to the inducer [132]. The boundary between genes responding and non-responding to RA induction is at the level of the ninth paralogous group (Fig.…”

Section: Regulation Of Hox Genes By Retinoids: the Embryonal Carcinommentioning

confidence: 99%

Regulation of vertebrate homeobox‐containing genes by morphogens

Mavilio

1993

European Journal of Biochemistry

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“…7 and 8), results in the sequential activation of several Hox genes in a manner that resembles their positions in the clusters, e.g. 3Ј genes are activated before 5Ј genes (7)(8)(9). Moreover, our laboratory discovered the presence of a retinoic acid response element (RARE) in the 3Ј enhancer of the Hoxa1 gene (10 -13).…”

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confidence: 99%

Differences in Gene Expression between Wild Type and Hoxa1 Knockout Embryonic Stem Cells after Retinoic Acid Treatment or Leukemia Inhibitory Factor (LIF) Removal

Martinez‐Ceballos

Chambon

Gudas

2005

Journal of Biological Chemistry

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Homeobox (Hox) genes encode a family of transcription factors that regulate embryonic patterning and organogenesis. In embryos, alterations of the normal pattern of Hox gene expression result in homeotic transformations and malformations. Disruption of the Hoxa1 gene, the most 3 member of the Hoxa cluster and a retinoic acid (RA) direct target gene, results in abnormal ossification of the skull, hindbrain, and inner ear deficiencies, and neonatal death. We have generated Hoxa1 genes positioned at the 3Ј-end are expressed earlier and more anterior, whereas 5Ј-end genes are expressed at later times and more posterior (reviewed in Refs. 1 and 5). Colinear gene expression from these Hox gene clusters may involve an initial change in chromatin structure (histone modification and chromatin decondensation) of the entire loci, which would then facilitate the programmed expression of genes along the clusters by a progressive 3Ј to 5Ј change in higher order chromatin structure (6). Treatment of teratocarcinoma cells or embryonic stem cells with retinoic acid (RA), which acts via the retinoic acid receptors (RAR␣, -␤, and -␥ and their isoforms (reviewed in Refs. 7 and 8), results in the sequential activation of several Hox genes in a manner that resembles their positions in the clusters, e.g. 3Ј genes are activated before 5Ј genes (7-9). Moreover, our laboratory discovered the presence of a retinoic acid response element (RARE) in the 3Ј enhancer of the Hoxa1 gene (10 -13). This RARE is also functional in transgenic mice (14 -16). We also demonstrated that unlike F9 Wt cells, F9 RAR␥ Ϫ/Ϫ cells fail to express the Hoxa1 gene in response to RA (17). Alterations in the normal pattern of Hox gene expression in embryos result in homeotic transformations and malformations, and frequently, in perinatal lethality (3,18). For instance, the targeted inactivation in mice of both alleles of the most 3Ј member of the Hoxa cluster, the Hoxa1 gene, leads to numerous developmental defects, including hindbrain deficiencies and abnormal skull ossification, and ultimately, to neonatal death (19 -22). Numerous studies have demonstrated that the hindbrain defects in Hoxa1 Ϫ/Ϫ mice result in part from the failure of Hoxb1 to reach its anterior limit of expression at the presumptive rhombomere 3/rhombomere 4 (r3/4) boundary, which initiates a cascade of gene misexpression that results in the misspecification of the hindbrain compartments from r2 to r5 (23-26). Furthermore, the ectopic expression of Hoxa1 in transgenic mice leads to the ectopic activation of Hoxb1 in r2, produces anterior abnormalities, including the reorganization of the developing hindbrain, and ultimately results in embryonic death (27). These observations highlight the importance of the Hoxa1 gene and suggest that the regulatory effects of retinoids on cell growth and on embryonic patterning may be * This work was supported by National Institutes of Health Grants R01CA43796 (to L. J. G.) and UR 2U19HDO35466. The costs of publication of this article were defrayed in part by th...

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Human HOX genes are differentially activated by retinoic acid in embryonal carcinoma cells according to their position within the four loci

Cited by 61 publications

References 44 publications

The pattern of expression of the chicken homolog of HOX1I in the developing limb suggests a possible role in the ectodermal inhibition of chondrogenesis

The pattern of expression of the chicken homolog of HOX1I in the developing limb suggests a possible role in the ectodermal inhibition of chondrogenesis

Regulation of vertebrate homeobox‐containing genes by morphogens

Differences in Gene Expression between Wild Type and Hoxa1 Knockout Embryonic Stem Cells after Retinoic Acid Treatment or Leukemia Inhibitory Factor (LIF) Removal

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