Two suppressors of<i>sel-12</i>encode C2H2zinc-finger proteins that regulate presenilin transcription in<i>Caenorhabditis elegans</i>

Lakowski, Bernard; Eimer, Stefan; Göbel, Christine; Böttcher, Alfred; Wagler, Babett; Baumeister, Ralf

doi:10.1242/dev.00429

Cited by 32 publications

(42 citation statements)

References 52 publications

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“…sel-12 is expressed strongly in all stages but most strongly in eggs. These results are similar to what we have seen by Northern blot [13] when we correct for the fact that the …”

Section: Sel-12(ptc) Transcripts Are Subject To Nmdsupporting

confidence: 90%

“…These screens are described in [11,13] however, only the isolation of strong spr mutations was reported in these papers. Additional weaker suppressors were also recovered in these screens but were not characterised at that time.…”

Section: Isolation Of Weak Spr Mutationsmentioning

confidence: 99%

“…SPR-1, SPR-3, SPR-4 and SPR-5 resemble components of the mammalian REST-CoREST transcriptional repressor complex [11][12][13]. Furthermore, SPR-1 physically interacts with SPR-5 in GST pull down and in yeast two hybrid experiments [11].…”

Section: Introductionmentioning

confidence: 98%

“…Six genes (spr-1-spr-5 and sel-10) have been identified that strongly suppress the sel-12 defects [9][10][11][12][13][14]. In the strongest suppressor mutations, the penetrance of sel-12 defects is reduced to less than 10% and in the spr-3 gene to almost 0% [13].…”

Section: Introductionmentioning

confidence: 99%

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Mutations in genes involved in nonsense mediated decay ameliorate the phenotype of sel-12 mutants with amber stop mutations in Caenorhabditis elegans

et al. 2009

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Background: Presenilin proteins are part of a complex of proteins that can cleave many type I transmembrane proteins, including Notch Receptors and the Amyloid Precursor Protein, in the middle of the transmembrane domain. Dominant mutations in the human presenilin genes PS1 and PS2 lead to Familial Alzheimer's disease. Mutations in the Caenorhabditis elegans sel-12 presenilin gene cause a highly penetrant egg-laying defect due to reduction of signalling through the lin-12/ Notch receptor. Mutations in six spr genes (for suppressor of presenilin) are known to strongly suppress sel-12. Mutations in most strong spr genes suppress sel-12 by de-repressing the transcription of the largely functionally equivalent hop-1 presenilin gene. However, how mutations in the spr-2 gene suppress sel-12 is unknown.

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“…sel-12 is expressed strongly in all stages but most strongly in eggs. These results are similar to what we have seen by Northern blot [13] when we correct for the fact that the …”

Section: Sel-12(ptc) Transcripts Are Subject To Nmdsupporting

confidence: 90%

Section: Isolation Of Weak Spr Mutationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mutations in genes involved in nonsense mediated decay ameliorate the phenotype of sel-12 mutants with amber stop mutations in Caenorhabditis elegans

et al. 2009

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“…The most likely of such mechanisms would involve a second rest or rest-like gene, as gene duplicates are common in zebrafish (Postlethwait et al, 2000). Functional similarities have been proposed between rest and several invertebrate genes including spr-3, spr-4, charlatan and tramtrack (Dallman et al, 2004;Lakowski et al, 2003;Tsuda et al, 2006). A zebrafish homolog of one of these factors might also compensate for loss of Rest function.…”

Section: Does Rest Function Differ In Zebrafish and Mouse?mentioning

confidence: 99%

Zebrafish rest regulates developmental gene expression but not neurogenesis

et al. 2012

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SUMMARYThe transcriptional repressor Rest (Nrsf) recruits chromatin-modifying complexes to RE1 'silencer elements', which are associated with hundreds of neural genes. However, the requirement for Rest-mediated transcriptional regulation of embryonic development and cell fate is poorly understood. Conflicting views of the role of Rest in controlling cell fate have emerged from recent studies. To address these controversies, we examined the developmental requirement for Rest in zebrafish using zinc-finger nucleasemediated gene targeting. We discovered that germ layer specification progresses normally in rest mutants despite derepression of target genes during embryogenesis. This analysis provides the first evidence that maternal rest is essential for repression of target genes during blastula stages. Surprisingly, neurogenesis proceeds largely normally in rest mutants, although abnormalities are observed within the nervous system, including defects in oligodendrocyte precursor cell development and a partial loss of facial branchiomotor neuron migration. Mutants progress normally through embryogenesis but many die as larvae (after 12 days). However, some homozygotes reach adulthood and are viable. We utilized an RE1/NRSE transgenic reporter system to dynamically monitor Rest activity. This analysis revealed that Rest is required to repress gene expression in mesodermal derivatives including muscle and notochord, as well as within the nervous system. Finally, we demonstrated that Rest is required for long-term repression of target genes in non-neural tissues in adult zebrafish. Our results point to a broad role for Rest in fine-tuning neural gene expression, rather than as a widespread regulator of neurogenesis or cell fate.

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The chromatin modifying complex CoREST/LSD1 negatively regulates notch pathway during cerebral cortex development

Lopez

Saud

Aguilar

et al. 2016

Developmental Neurobiology

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The development of the cerebral cortex is a dynamic and coordinated process in which cell division, cell death, migration, and differentiation must be highly regulated to acquire the final architecture and functional competence of the mature organ. Notch pathway is an important regulator of differentiation and it is essential to maintain neural stem cell (NSC) pool. Here, we studied the role of epigenetic modulators such as lysine-specific demethylase 1 (LSD1) and its interactor CoREST in the regulation of the Notch pathway activity during the development of the cerebral cortex. We found that CoREST and LSD1 interact in vitro with RBPJ-κ in the repressor complex and these proteins are released upon overexpression of Notch intracellular domain (NICD). We corroborated LSD1 and RBPJ-κ interaction in developing cerebral cortex and also found that LSD1 binds to the hes1 promoter. Knock-down of CoREST and LSD1 by in utero electroporation increases Hes1 expression in vivo and decreases Ngn2. Interestingly, we found a functional interaction between CoREST and LSD1 with Notch pathway. This conclusion is based on the observation that both the defects in neuronal migration and the increase in the number of cells expressing Sox2 and Tbr2 were associated to the knock-down of either CoREST or LSD1 and were reversed by the loss of Notch. These results demonstrate that CoREST and LSD1 downregulate the Notch pathway in the developing cerebral cortex, thus suggesting a role of epigenetic regulation in the fine tuning of cell differentiation. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1360-1373, 2016.

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Two suppressors ofsel-12encode C2H2zinc-finger proteins that regulate presenilin transcription inCaenorhabditis elegans

Abstract: Mutations in presenilin genesSupplemental data available online

Cited by 32 publications

References 52 publications

Mutations in genes involved in nonsense mediated decay ameliorate the phenotype of sel-12 mutants with amber stop mutations in Caenorhabditis elegans

Mutations in genes involved in nonsense mediated decay ameliorate the phenotype of sel-12 mutants with amber stop mutations in Caenorhabditis elegans

Zebrafish rest regulates developmental gene expression but not neurogenesis

The chromatin modifying complex CoREST/LSD1 negatively regulates notch pathway during cerebral cortex development

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