Drosophila Keap1 xenobiotic response factor regulates developmental transcription through binding to chromatin

Carlson, Jennifer H.; Price, Lindsey; Cook, Isabel; Huai, Dongxin

doi:10.1016/j.ydbio.2021.10.003

Cited by 5 publications

(8 citation statements)

References 49 publications

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“…Considering that RAS is necessary for PTTH signaling ( Rewitz et al, 2009b ; Pan et al, 2020 ; Kannangara et al, 2021 ), CncC seems to be downstream of the PTTH-RAS pathway. In addition, a more recent study has also found that loss of function of Keap1 results in the reduction in the expression of several Halloween genes in the ovary, another ecdysteroid biosynthetic organ ( Carlson et al, 2022 ).…”

Section: Transcription Factors To Regulate the Expression Of Hallowee...mentioning

confidence: 99%

Transcriptional Regulators of Ecdysteroid Biosynthetic Enzymes and Their Roles in Insect Development

Kamiyama

Niwa

2022

Front. Physiol.

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Steroid hormones are responsible for coordinating many aspects of biological processes in most multicellular organisms, including insects. Ecdysteroid, the principal insect steroid hormone, is biosynthesized from dietary cholesterol or plant sterols. In the last 20 years, a number of ecdysteroidogenic enzymes, including Noppera-bo, Neverland, Shroud, Spook/Spookier, Cyp6t3, Phantom, Disembodied, Shadow, and Shade, have been identified and characterized in molecular genetic studies using the fruit fly Drosophila melanogaster. These enzymes are encoded by genes collectively called the Halloween genes. The transcriptional regulatory network, governed by multiple regulators of transcription, chromatin remodeling, and endoreplication, has been shown to be essential for the spatiotemporal expression control of Halloween genes in D. melanogaster. In this review, we summarize the latest information on transcriptional regulators that are crucial for controlling the expression of ecdysteroid biosynthetic enzymes and their roles in insect development.

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Section: Transcription Factors To Regulate the Expression Of Hallowee...mentioning

confidence: 99%

Transcriptional Regulators of Ecdysteroid Biosynthetic Enzymes and Their Roles in Insect Development

Kamiyama

Niwa

2022

Front. Physiol.

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“…Expressing fusions of dKeap1 N-terminal deletion (YFP-dKeap1-ΔNTD) or C-terminal deletion (YFP-dKeap1-ΔCTD) had no or only moderate effect on Lamin distribution. YFP-dKeap1-ΔCTD localized almost exclusively to the cytoplasm (Fig 2B) (Carlson et al ., 2022). YFP-dKeap1-ΔNTD localized to both the cytoplasm and nucleus, and the ratio of different portions varied in different cells (Fig 2B).…”

Section: Resultsmentioning

confidence: 83%

“…Intrinsic dKeap1 proteins localized to both the nucleoplasm and the nuclear lamina, while none of the dKeap1 fusion proteins showed localization to the nuclear lamina (Fig 1A, 2B), indicating that the YFP-dKeap1 fusion proteins cannot function the same as intrinsic dKeap1 proteins in the nuclear lamina. In support of this, overexpression of YFP-dKeap1-FL largely but cannot fully rescue the viability and fertility of the dKeap1 null mutant (Carlson et al ., 2022). It is possible that the HA-YFP tag interferes with the interaction between dKeap1 and Lamin.…”

Section: Resultsmentioning

confidence: 96%

“…Interestingly, conditional expression of Lamin or Kugelkern in Drosophila adult tissues reduces the lifespan and causes wrinkled and lobulated nuclear shapes (Brandt et al 2008). Overexpression of dKeap1 fusion proteins allowed the early lethal dKeap1 null mutants to survive to adults, but the rescue was only partial, and these flies showed reduced fertility (Carlson et al ., 2022). We hypothesize that this developmental defect is associated with the disrupted lamina structure and the consequent mis-organization of chromatin and mis-regulation of developmental genes.…”

Section: Resultsmentioning

confidence: 99%

“…Keap1 and Nrf2 can also directly regulate transcription of developmental genes. For example, mouse Nrf2 and Drosophila dKeap1 both regulate adipogenesis through controlling adipogenesis genes (Carlson et al , 2022; Huang et al , 2010; Kim et al , 2018; Pi et al , 2010). Mouse Nrf2 also promotes cell proliferation by transcriptional activation of glucose metabolic enzymes (Mitsuishi et al , 2012) and promotes neuronal stem cell differentiation by activating genes that inhibit self-renewal (Khacho et al , 2016).…”

Section: Introductionmentioning

confidence: 99%

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Drosophila Keap1 oxidative/xenobiotic response factor interacts with B-type lamin to regulate nuclear lamina and heterochromatin

Carlson

Neidviecky

Cook

et al. 2022

Preprint

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The essential function of the Keap1-Nrf2 pathway in mediating transcriptional response to xenobiotic and oxidative stimuli has been well established. However, the mechanisms whereby Keap1 and Nrf2 regulate developmental genes remains unclear. We hypothesized that Drosophila Keap1 (dKeap1) and Nrf2 (CncC) proteins regulate transcription through controlling high-order chromatin structure. Here, we describe evidence supporting that dKeap1 can regulate chromatin through interaction with lamin, the intermediate filament proteins that form nuclear lamina and organize the overall chromatin architecture. dKeap1 and lamin Dm0, the B-type lamin in Drosophila, interact with each other and form complexes in the nucleus. Overexpression of dKeap1 resulted in a redistribution of lamin Dm0 to the intra-nuclear area and consistently, caused a spreading of the heterochromatin marker H3K9me2 from the pericentromeric region to chromosome arms. Overexpression of dKeap1 fusion proteins in the dKeap1 null background significantly disrupted the nuclear lamina morphology, indicating that dKeap1 is required for the maintenance of a normal nuclear lamina. Knock down of dKeap1 partially rescued the lethality caused by lamin Dm0 overexpression, suggesting that dKeap1 and lamin Dm0 function in the same pathway during development. Taken together, these results support a model where dKeap1 regulates chromatin structure and developmental transcription through interaction with lamin proteins, revealing a novel epigenetic function of the Keap1 oxidative/xenobiotic response factor.

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Interaction with B-type lamin reveals the function of Drosophila Keap1 xenobiotic response factor in nuclear architecture

Carlson,

Neidviecky,

Cook

et al. 2024

Mol Biol Rep

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Drosophila Keap1 xenobiotic response factor regulates developmental transcription through binding to chromatin

Cited by 5 publications

References 49 publications

Transcriptional Regulators of Ecdysteroid Biosynthetic Enzymes and Their Roles in Insect Development

Transcriptional Regulators of Ecdysteroid Biosynthetic Enzymes and Their Roles in Insect Development

Drosophila Keap1 oxidative/xenobiotic response factor interacts with B-type lamin to regulate nuclear lamina and heterochromatin

Interaction with B-type lamin reveals the function of Drosophila Keap1 xenobiotic response factor in nuclear architecture

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