Identification of proteins interacting with Toxoplasma SRCAP by yeast two-hybrid screening

Nallani, Karuna; Sullivan, William J.

doi:10.1007/s00436-004-1291-5

Cited by 12 publications

(3 citation statements)

References 23 publications

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“…The N-CoR complex also contains components of the SWI/SNF chromatin-remodeling complex, and SMARCB1 was previously proven to interact with N-CoR, indicating a potential functional link between LZTR1 and SMARCB1 or other members of the SWI/SNF complex 32 . Moreover, studies in the evolutionarily distant organism Toxoplasma gondii have shown that the Toxoplasma homolog of LZTR1 interacts with SRCAP 33 , another member of the SWI/SNF complex.…”

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Germline loss-of-function mutations in LZTR1 predispose to an inherited disorder of multiple schwannomas

et al. 2013

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Constitutional SMARCB1 mutations at 22q11.23 have been found in ~50% of familial and <10% of sporadic schwannomatosis cases1. We sequenced highly conserved regions along 22q from eight individuals with schwannomatosis whose schwannomas involved somatic loss of one copy of 22q, encompassing SMARCB1 and NF2, with a different somatic mutation of the other NF2 allele in every schwannoma but no mutation of the remaining SMARCB1 allele in blood and tumor samples. LZTR1 germline mutations were identified in seven of the eight cases. LZTR1 sequencing in 12 further cases with the same molecular signature identified 9 additional germline mutations. Loss of heterozygosity with retention of an LZTR1 mutation was present in all 25 schwannomas studied. Mutations segregated with disease in all available affected first-degree relatives, although four asymptomatic parents also carried an LZTR1 mutation. Our findings identify LZTR1 as a gene predisposing to an autosomal dominant inherited disorder of multiple schwannomas in ~80% of 22q-related schwannomatosis cases lacking mutation in SMARCB1.

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Germline loss-of-function mutations in LZTR1 predispose to an inherited disorder of multiple schwannomas

et al. 2013

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“…A number of zinc finger proteins are also evident in apicomplexan genomes that may have DNA-binding activity. Finally, TgLZTR was isolated from a yeast two-hybrid screen using a portion of TgSRCAP as bait [51]. TgLZTR is a predicted Leucine Zipper-like Transcriptional Regulator (TGME49_098600/125.m00070), but it has not been demonstrated to be a functional TF at present.…”

Section: Questions For the Next Decade And Beyondmentioning

confidence: 99%

A decade of epigenetic research in Toxoplasma gondii

Dixon

Stilger

Elias

et al. 2010

Molecular and Biochemical Parasitology

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In the past ten years, the field of parasitology has witnessed an explosion of studies investigating gene regulation. In this review, we will describe recent advances largely stemming from the study of Toxoplasma gondii, a significant opportunistic pathogen and useful model for other apicomplexan protozoa. Surprising findings have emerged, including the discovery of a wealth of epigenetic machinery in these primitive eukaryotes, unusual histone variants, and a battery of plant-like transcription factors. We will elaborate on how these unusual features impact parasite physiology and potential therapeutics as we summarize some of the key discoveries from the last decade. We will close by proposing a few questions to address in the next ten years.

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“…The RSC complex can act in response to stress and target promoters of stress-responsive genes [16]. Members of these complexes have been identified in T. gondii , including Snf2-related CBP activator protein TgSRCAP [17]. In this study, we describe characterization of an insertional mutant in TgRSC8 , a locus showing homology to yeast paralogs Swi3p and Rsc8p of SWI/SNF and RSC complexes, respectively.…”

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confidence: 99%

Involvement of a Toxoplasma gondii Chromatin Remodeling Complex Ortholog in Developmental Regulation

2011

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The asexual cycle of the parasite Toxoplasma gondii has two developmental stages: a rapidly replicating form called a tachyzoite and a slow growing cyst form called a bradyzoite. While the importance of ATP-independent histone modifications for gene regulation in T. gondii have been demonstrated, ATP-dependent chromatin remodeling pathways have not been examined. In this study we characterized C9, an insertional mutant showing reduced expression of bradyzoite differentiation marker BAG1, in cultured human fibroblasts. This mutant contains an insertion in the gene encoding TgRSC8, which is homologous to the Saccharomyces cerevisiae proteins Rsc8p (remodel the structure of chromatin complex subunit 8) and Swi3p (switch/sucrose non-fermentable [SWI/SNF]) of ATP-dependent chromatin-remodeling complexes. In the C9 mutant, TgRSC8 is the downstream open reading frame on a dicistronic transcript. Though protein was expressed from the downstream gene of the dicistron, TgRSC8 levels were decreased in C9 from those of wild-type parasites, as determined by western immunoblot and flow cytometry. As TgRSC8 localized to the parasite nucleus, we postulated a role in gene regulation. Transcript levels of several markers were assessed by quantitative PCR to test this hypothesis. The C9 mutant displayed reduced steady state transcript levels of bradyzoite-induced genes BAG1, LDH2, SUSA1, and ENO1, all of which were significantly increased with addition of TgRSC8 to the mutant. Transcript levels of some bradyzoite markers were unaltered in C9, or unable to be increased by complementation with TgRSC8, indicating multiple pathways control bradyzoite-upregulated genes. Together, these data suggest a role for TgRSC8 in control of bradyzoite-upregulated gene expression. Thus chromatin remodeling, by both ATP-independent and dependent mechanisms, is an important mode of gene regulation during stage differentiation in parasites.

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Identification of proteins interacting with Toxoplasma SRCAP by yeast two-hybrid screening

Cited by 12 publications

References 23 publications

Germline loss-of-function mutations in LZTR1 predispose to an inherited disorder of multiple schwannomas

Germline loss-of-function mutations in LZTR1 predispose to an inherited disorder of multiple schwannomas

A decade of epigenetic research in Toxoplasma gondii

Involvement of a Toxoplasma gondii Chromatin Remodeling Complex Ortholog in Developmental Regulation

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