"The ubiquitin ligase SIAH2 is a female-specific regulator of circadian rhythms and metabolism".
Circadian clocks enable organisms to predict and align their behaviors and physiologies to constant daily day-night environmental cycle. Because the ubiquitin ligase Siah2 has been identified as a potential regulator of circadian clock function in cultured cells, we have used SIAH2-deficient mice to...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-07-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1010305 |
| _version_ | 1818161260911394816 |
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| author | Tsedey Mekbib Ting-Chung Suen Aisha Rollins-Hairston Kiandra Smith Ariel Armstrong Cloe Gray Sharon Owino Kenkichi Baba Julie E Baggs J Christopher Ehlen Gianluca Tosini Jason P DeBruyne |
| author_facet | Tsedey Mekbib Ting-Chung Suen Aisha Rollins-Hairston Kiandra Smith Ariel Armstrong Cloe Gray Sharon Owino Kenkichi Baba Julie E Baggs J Christopher Ehlen Gianluca Tosini Jason P DeBruyne |
| author_sort | Tsedey Mekbib |
| collection | DOAJ |
| description | Circadian clocks enable organisms to predict and align their behaviors and physiologies to constant daily day-night environmental cycle. Because the ubiquitin ligase Siah2 has been identified as a potential regulator of circadian clock function in cultured cells, we have used SIAH2-deficient mice to examine its function in vivo. Our experiments demonstrate a striking and unexpected sexually dimorphic effect of SIAH2-deficiency on the regulation of rhythmically expressed genes in the liver. The absence of SIAH2 in females, but not in males, altered the expression of core circadian clock genes and drastically remodeled the rhythmic transcriptome in the liver by increasing the number of day-time expressed genes, and flipping the rhythmic expression from nighttime expressed genes to the daytime. These effects are not readily explained by effects on known sexually dimorphic pathways in females. Moreover, loss of SIAH2 in females, not males, preferentially altered the expression of transcription factors and genes involved in regulating lipid and lipoprotein metabolism. Consequently, SIAH2-deficient females, but not males, displayed disrupted daily lipid and lipoprotein patterns, increased adiposity and impaired metabolic homeostasis. Overall, these data suggest that SIAH2 may be a key component of a female-specific circadian transcriptional output circuit that directs the circadian timing of gene expression to regulate physiological rhythms, at least in the liver. In turn, our findings imply that sex-specific transcriptional mechanisms may closely interact with the circadian clock to tailor overt rhythms for sex-specific needs. |
| first_indexed | 2024-12-11T16:14:57Z |
| format | Article |
| id | doaj.art-be0a2af3db4e4fe7b9abc59d1a0f7b5d |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-11T16:14:57Z |
| publishDate | 2022-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-be0a2af3db4e4fe7b9abc59d1a0f7b5d2022-12-22T00:58:59ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042022-07-01187e101030510.1371/journal.pgen.1010305"The ubiquitin ligase SIAH2 is a female-specific regulator of circadian rhythms and metabolism".Tsedey MekbibTing-Chung SuenAisha Rollins-HairstonKiandra SmithAriel ArmstrongCloe GraySharon OwinoKenkichi BabaJulie E BaggsJ Christopher EhlenGianluca TosiniJason P DeBruyneCircadian clocks enable organisms to predict and align their behaviors and physiologies to constant daily day-night environmental cycle. Because the ubiquitin ligase Siah2 has been identified as a potential regulator of circadian clock function in cultured cells, we have used SIAH2-deficient mice to examine its function in vivo. Our experiments demonstrate a striking and unexpected sexually dimorphic effect of SIAH2-deficiency on the regulation of rhythmically expressed genes in the liver. The absence of SIAH2 in females, but not in males, altered the expression of core circadian clock genes and drastically remodeled the rhythmic transcriptome in the liver by increasing the number of day-time expressed genes, and flipping the rhythmic expression from nighttime expressed genes to the daytime. These effects are not readily explained by effects on known sexually dimorphic pathways in females. Moreover, loss of SIAH2 in females, not males, preferentially altered the expression of transcription factors and genes involved in regulating lipid and lipoprotein metabolism. Consequently, SIAH2-deficient females, but not males, displayed disrupted daily lipid and lipoprotein patterns, increased adiposity and impaired metabolic homeostasis. Overall, these data suggest that SIAH2 may be a key component of a female-specific circadian transcriptional output circuit that directs the circadian timing of gene expression to regulate physiological rhythms, at least in the liver. In turn, our findings imply that sex-specific transcriptional mechanisms may closely interact with the circadian clock to tailor overt rhythms for sex-specific needs.https://doi.org/10.1371/journal.pgen.1010305 |
| spellingShingle | Tsedey Mekbib Ting-Chung Suen Aisha Rollins-Hairston Kiandra Smith Ariel Armstrong Cloe Gray Sharon Owino Kenkichi Baba Julie E Baggs J Christopher Ehlen Gianluca Tosini Jason P DeBruyne "The ubiquitin ligase SIAH2 is a female-specific regulator of circadian rhythms and metabolism". PLoS Genetics |
| title | "The ubiquitin ligase SIAH2 is a female-specific regulator of circadian rhythms and metabolism". |
| title_full | "The ubiquitin ligase SIAH2 is a female-specific regulator of circadian rhythms and metabolism". |
| title_fullStr | "The ubiquitin ligase SIAH2 is a female-specific regulator of circadian rhythms and metabolism". |
| title_full_unstemmed | "The ubiquitin ligase SIAH2 is a female-specific regulator of circadian rhythms and metabolism". |
| title_short | "The ubiquitin ligase SIAH2 is a female-specific regulator of circadian rhythms and metabolism". |
| title_sort | the ubiquitin ligase siah2 is a female specific regulator of circadian rhythms and metabolism |
| url | https://doi.org/10.1371/journal.pgen.1010305 |
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