1 Homeobox Genes in Cardiovascular Development

Patterson, Kristin D.; Cleaver, Ondine; Gerber, Wendy V.; Grow, Matthew W.; Newman, Christopher; Krieg, Paul A.

doi:10.1016/s0070-2153(08)60363-4

Cited by 20 publications

(7 citation statements)

References 172 publications

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“…PRH has been identified as a member of the NK (nuclear body-associated kinase) subclass of homeodomain proteins that carry a TN (tinman) motif [24,25]. The TN motif is a conserved decapeptide sequence (TPFSVKDILNLE) found N-terminally to the homeodomain in homeoproteins that are involved in heart development [26].…”

Section: Prh Proteinmentioning

confidence: 99%

PRH/Hex: an oligomeric transcription factor and multifunctional regulator of cell fate

Soufi

Jayaraman

2008

Biochemical Journal

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The PRH (proline-rich homeodomain) [also known as Hex (haematopoietically expressed homeobox)] protein is a critical regulator of vertebrate development. PRH is able to regulate cell proliferation and differentiation and is required for the formation of the vertebrate body axis, the haematopoietic and vascular systems and the formation of many vital organs. PRH is a DNA-binding protein that can repress and activate the transcription of its target genes using multiple mechanisms. In addition, PRH can regulate the nuclear transport of specific mRNAs making PRH a member of a select group of proteins that control gene expression at the transcriptional and translational levels. Recent biophysical analysis of the PRH protein has shown that it forms homo-oligomeric complexes in vivo and in vitro and that the proline-rich region of PRH forms a novel dimerization interface. Here we will review the current literature on PRH and discuss the complex web of interactions centred on this multifunctional protein.

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Section: Prh Proteinmentioning

confidence: 99%

PRH/Hex: an oligomeric transcription factor and multifunctional regulator of cell fate

Soufi

Jayaraman

2008

Biochemical Journal

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“…PRH is expressed in the anterior endoderm in developing Xenopus and mouse embryos (11,12) and is present in fetal liver, thyroid, and lung (13). It is a member of the tinman family of homeodomain-containing proteins that includes several transcription factors essential for the development of cardiac tissue (14). Within the hematopoietic compartment PRH mRNA is expressed in B-cells, myelomonocytic cells, and erythroid cells but not in T-cell lineages (7,15), and in general, PRH mRNA levels are down-regulated as hematopoietic cells differentiate (15,16).…”

mentioning

confidence: 99%

PRH Represses Transcription in Hematopoietic Cells by at Least Two Independent Mechanisms

Guiral

Bess

Goodwin

et al. 2001

Journal of Biological Chemistry

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PRH (proline-rich homeodomain protein) is strongly expressed in the hematopoietic compartment. Here we show that PRH is a repressor of transcription in hematopoietic cells. A fragment of PRH that includes the homeodomain can bind to TATA box sequences in vitro and can also bind to the TATA box-binding protein. PRH represses transcription from TATA box-containing promoters in intact cells but does not repress transcription from a promoter lacking a TATA box. A mutation in the PRH homeodomain that blocks binding to DNA but that has little or no effect on binding to the TATA box-binding protein significantly reduces the ability of the protein to repress transcription and provides the first clear demonstration that a homeodomain can bring about transcriptional repression in vivo by binding to a TATA box. However, we also show that mutation of the PRH homeodomain does not block the ability of PRH to repress transcription when this protein is tethered upstream of the TATA box via a heterologous DNA-binding domain. PRH also contains an N-terminal proline-rich repression domain that is separate from the homeodomain. Deletion mapping suggests that this repression domain contains at least two regions that both independently contribute to transcriptional repression.

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“…(HNF3-?b) [32], many of them involved in lung morphogenesis. At the same time, some of the homeobox genes are essential for normal cardiovascular development [23]. That is why our experiments were focused on the expression of the four proximal Hox genes in the lungs and in the hearts of EA animals.…”

Section: Discussionmentioning

confidence: 99%

“…Most of them follow a pattern that resembles a neural crest dysfunction, both in humans and animals [21,22]. Homeotic genes are involved not only in cardiac development [23], but also in the migration of neural crest cells throughout the pharyngeal pouches and arches that give rise to many cardiac structures [17], so it is likely that their expression can be abnormal in the hearts of EA patientes.…”

Section: Introductionmentioning

confidence: 99%

Expression of homeotic genes Hoxa3, Hoxb3, Hoxd3 and Hoxc4 is decreased in the lungs but not in the hearts of adriamycin-exposed mice

et al. 2007

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Exposure of rat and mouse embryos to adriamycin (doxorubicin chlorhydrate) induces esophageal atresia (EA) and VACTERL association. Sonic hedgehog (Shh) and Gli2/Gli3 pathways are involved in these conditions and knockout mice for homeotic Hox genes Hoxa3, Hoxb3, Hoxc3, Hoxc4 and Hoxa5 show phenotypes with some of the associated VACTERL features. This study aims at evaluating the possible influence of Hoxa3, Hoxb3, Hoxd3 and Hoxc4 as upstream regulators of this complex signalling. Pregnant mice were exposed either to 4 mg/kg of adriamycin (EA group) or vehicle (controls) on embryonic days 7.5 and 8.5. Embryos were recovered at four endpoints (E12.5-E15.5) and randomly assigned for immunohistochemical or molecular biology studies. Lungs and hearts were separately harvested and processed for Hoxa3, Hoxb3, Hoxd3 and Hoxc4 quantitative RT-PCR measurements. Antibodies for Hoxa3, Hoxb3 and Hoxd3 proteins were used for immunohistochemical studies. RT-PCR studies showed a drastic and statistically significant decrease of the four genes in the lungs of EA mice when compared to controls, with a slight recovery from E15.5. Hearts of both groups showed a similar expression of all the genes throughout gestation. Control embryos expressed the hox3 paralogous genes in heart, skin, foregut derivatives and their surrounding mesoderm through E12.5-E15.5 whereas adriamycin-exposed embryos showed a severe decrease in expression of these three proteins in the same tissues but not in the heart. Adriamycin drastically reduced the expression of Hoxa3, Hoxb3, Hoxd3 and Hoxc4 in mice embryonic lungs. Their expression in the heart did not seem to be influenced by adriamycin in this experimental setting.

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1 Homeobox Genes in Cardiovascular Development

Cited by 20 publications

References 172 publications

PRH/Hex: an oligomeric transcription factor and multifunctional regulator of cell fate

PRH/Hex: an oligomeric transcription factor and multifunctional regulator of cell fate

PRH Represses Transcription in Hematopoietic Cells by at Least Two Independent Mechanisms

Expression of homeotic genes Hoxa3, Hoxb3, Hoxd3 and Hoxc4 is decreased in the lungs but not in the hearts of adriamycin-exposed mice

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