A new role for hth in the early pre-blastodermic divisions in drosophila

Salvany, Lara; Aldaz, Silvia; Corsetti, Elise; Azpiazu, Natalia

doi:10.4161/cc.8.17.9388

Cited by 24 publications

(33 citation statements)

References 45 publications

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“…This result is not surprising, due to the fact that the primers used recognize the three Flhth, the hthRG and the maternal component (Salvany et al, 2009). The amount of hthRG, although detectable, is approximately 125 times less abundant than that of the Flhth and 16 times less represented than the hthRF (see Fig.…”

Section: Relative Amounts Of the Different Hth Isoforms In Wild-type mentioning

confidence: 55%

“…As expected, Dfhth mutants show neither hthRE nor hthRF transcripts and the levels of the full-length isoforms are very much reduced. We still observed some Flhth transcripts in the mutants that we believe are of maternal origin (Salvany et al, 2009) and the remaining hthRG (note that the primers used to amplify the Flhth transcripts also recognize the hthRG, see Materials and methods). hthRG shows a mild reduction of 1.2 times in the mutant background.…”

Section: Contribution Of the Different Isoforms To Normal Developmentmentioning

confidence: 91%

“…That hth/exd have these additional functions is not totally unexpected since hth and exd encode transcription factors that regulate the transcriptional activity of specific targets genes. However, an unexpected role for hth in centric heterochromatin assembly in early embryos has been recently described (Salvany et al, 2009). The versatility that these transcription factors display throughout the development correlates with a high complexity in the hth locus.…”

Section: Introductionmentioning

confidence: 97%

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Functional dissection of the splice variants of the Drosophila gene homothorax (hth)

Corsetti

Azpiazu

2013

Developmental Biology

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Homothorax belongs to the TALE-homeodomain family of transcription factors, together with its vertebrate counterparts, the Meis family of proto-oncogenes. It fulfills many important different functions during embryonic and larval developments in Drosophila, which encompass from subdivision and specification of body parts to assembly of heterochromatin structures. Hth interacts with Extradenticle, another member of the TALE-homeodomain family of conserved transcription factors, to facilitate its entrance to the nucleus. The many different functions described for Hth rely on the complexity of the locus, from which six different isoforms arise. The isoforms can be grouped into full-length and short versions, which contain either one or the two conserved domains of the protein (homeodomain and Exd-interacting domain). We have used molecular and genetic tools to analyze the levels of expression, the distribution and the function of the isoforms during embryonic development. Our results clearly show that the isoforms display distinct levels of expression and are differentially distributed in the embryo. This detailed study also shows that during normal embryonic development not all the Hth isoforms translocate Exd into the nucleus, suggesting that both the proteins can also function separately. We have demonstrated that the full-length Hth protein activates transcription of exd, augmenting the levels of exd mRNA in the cell. The higher levels of Exd protein in those cells facilitate its entrance to the nucleus. Our work demonstrates that hth is a complex gene that should not be considered as a functional unit. The roles of the different isoforms probably rely on their distinct protein domains and conformations and, at the end, on interactions with particular partners.

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Section: Relative Amounts Of the Different Hth Isoforms In Wild-type mentioning

confidence: 55%

Section: Contribution Of the Different Isoforms To Normal Developmentmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 97%

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Functional dissection of the splice variants of the Drosophila gene homothorax (hth)

Corsetti

Azpiazu

2013

Developmental Biology

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“…The effect of Prep1 down-regulation on chromatin methylation and expression of the satellite DNA might suggest a possible mechanism. In Drosophila, the deletion of the single ortholog of both Prep and Meis, Hth, is accompanied by chromosomal instability and loss of transcription of pericentric satellite repeats (45). However, the effects of Prep1 and Hth are different; whereas Hth physically interacts with RNA PolII in the satellite regions, Prep1 does not bind to pericentric major satellites (Fig.…”

Section: Discussionmentioning

confidence: 99%

Homeodomain transcription factor and tumor suppressor Prep1 is required to maintain genomic stability

Iotti

Longobardi

Masella

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Prep1 is a homeodomain transcription factor that is essential in embryonic development and functions in the adult as a tumor suppressor. We show here that Prep1 is involved in maintaining genomic stability and preventing neoplastic transformation. Hypomorphic homozygous Prep1 i/i fetal liver cells and mouse embryonic fibroblasts (MEFs) exhibit increased basal DNA damage and normal DNA damage response after γ-irradiation compared with WT. Cytogenetic analysis shows the presence of numerous chromosomal aberrations and aneuploidy in very early-passage Prep1 i/i MEFs. In human fibroblasts, acute Prep1 down-regulation by siRNA induces DNA damage response, like in Prep1 i/i MEFs, together with an increase in heterochromatin-associated modifications: rapid increase of histone methylation and decreased transcription of satellite DNA. Ectopic expression of Prep1 rescues DNA damage and heterochromatin methylation. Inhibition of Suv39 activity blocks the chromatin but not the DNA damage phenotype. Finally, Prep1 deficiency facilitates cell immortalization, escape from oncogeneinduced senescence, and H-Ras V12 -dependent transformation. Importantly, the latter can be partially rescued by restoration of Prep1 level. The results show that the tumor suppressor role of Prep1 is associated with the maintenance of genomic stability.

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“…Moreover, alterations in the abundance of cencRNAs have important consequences in H3K9 methylation, a modification whose regulation is essential for their own transcription [37, 41, 43, 67], demonstrating an interesting feedback loop that is worthy of further study.…”

Section: Mechanisms Of Regulating Centromere Function By Centromeric mentioning

confidence: 99%

Centromeric Non-coding Transcription: Opening the Black Box of Chromosomal Instability?

Cáceres-Gutiérrez

Herrera²

2017

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In eukaryotes, mitosis is tightly regulated to avoid the generation of numerical chromosome aberrations, or aneuploidies. The aneuploid phenotype is a consequence of chromosomal instability (CIN), i.e., an enhanced rate of chromosome segregation errors, which is frequently found in cancer cells and is associated with tumor aggressiveness and increased tumor cell survival potential. To avoid the generation of aneuploidies, cells rely on the spindle assembly checkpoint (SAC), a widely conserved mechanism that protects the genome against this type of error. This signaling pathway stops mitotic pro-gression before anaphase until all chromosomes are correctly attached to spindle microtubules. Howev-er, impairment of the SAC cannot account for the establishment of CIN because cells bearing this phe-notype have a functional SAC. Hence, in cells with CIN, anaphase is not triggered until all chromo-somes are correctly attached to spindle microtubules and congressed at the metaphase plate. Thus, an in-teresting question arises: What mechanisms actually mediate CIN in cancer cells? Recent research has shown that some pathways involved in chromosome segregation are closely associated to centromere-encoded non-coding RNA (cencRNA) and that these RNAs are deregulated in abnormal conditions, such as cancer. These mechanisms may provide new explanations for chromosome segregation errors. The present review discusses some of these findings and proposes novel mechanisms for the establish-ment of CIN based on regulation by cencRNA.

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A new role for hth in the early pre-blastodermic divisions in drosophila

Cited by 24 publications

References 45 publications

Functional dissection of the splice variants of the Drosophila gene homothorax (hth)

Functional dissection of the splice variants of the Drosophila gene homothorax (hth)

Homeodomain transcription factor and tumor suppressor Prep1 is required to maintain genomic stability

Centromeric Non-coding Transcription: Opening the Black Box of Chromosomal Instability?

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