Developmental regulation of neuronal gene expression by Elongator complex protein 1 dosage

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Standard

Developmental regulation of neuronal gene expression by Elongator complex protein 1 dosage. / Morini, Elisabetta; Gao, Dadi; Logan, Emily M.; Salani, Monica; Krauson, Aram J.; Chekuri, Anil; Chen, Yei Tsung; Ragavendran, Ashok; Chakravarty, Probir; Erdin, Serkan; Stortchevoi, Alexei; Svejstrup, Jesper Q.; Talkowski, Michael E.; Slaugenhaupt, Susan A.

I: Journal of Genetics and Genomics, Bind 49, Nr. 7, 2022, s. 654-665.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Morini, E, Gao, D, Logan, EM, Salani, M, Krauson, AJ, Chekuri, A, Chen, YT, Ragavendran, A, Chakravarty, P, Erdin, S, Stortchevoi, A, Svejstrup, JQ, Talkowski, ME & Slaugenhaupt, SA 2022, 'Developmental regulation of neuronal gene expression by Elongator complex protein 1 dosage', Journal of Genetics and Genomics, bind 49, nr. 7, s. 654-665. https://doi.org/10.1016/j.jgg.2021.11.011

APA

Morini, E., Gao, D., Logan, E. M., Salani, M., Krauson, A. J., Chekuri, A., Chen, Y. T., Ragavendran, A., Chakravarty, P., Erdin, S., Stortchevoi, A., Svejstrup, J. Q., Talkowski, M. E., & Slaugenhaupt, S. A. (2022). Developmental regulation of neuronal gene expression by Elongator complex protein 1 dosage. Journal of Genetics and Genomics, 49(7), 654-665. https://doi.org/10.1016/j.jgg.2021.11.011

Vancouver

Morini E, Gao D, Logan EM, Salani M, Krauson AJ, Chekuri A o.a. Developmental regulation of neuronal gene expression by Elongator complex protein 1 dosage. Journal of Genetics and Genomics. 2022;49(7):654-665. https://doi.org/10.1016/j.jgg.2021.11.011

Author

Morini, Elisabetta ; Gao, Dadi ; Logan, Emily M. ; Salani, Monica ; Krauson, Aram J. ; Chekuri, Anil ; Chen, Yei Tsung ; Ragavendran, Ashok ; Chakravarty, Probir ; Erdin, Serkan ; Stortchevoi, Alexei ; Svejstrup, Jesper Q. ; Talkowski, Michael E. ; Slaugenhaupt, Susan A. / Developmental regulation of neuronal gene expression by Elongator complex protein 1 dosage. I: Journal of Genetics and Genomics. 2022 ; Bind 49, Nr. 7. s. 654-665.

Bibtex

@article{2b9c57f71c114334bf4f0c7b3b1302d6,

title = "Developmental regulation of neuronal gene expression by Elongator complex protein 1 dosage",

abstract = "Familial dysautonomia (FD), a hereditary sensory and autonomic neuropathy, is caused by a mutation in the Elongator complex protein 1 (ELP1) gene that leads to a tissue-specific reduction of ELP1 protein. Our work to generate a phenotypic mouse model for FD headed to the discovery that homozygous deletion of the mouse Elp1 gene leads to embryonic lethality prior to mid-gestation. Given that FD is caused by a reduction, not loss, of ELP1, we generated two new mouse models by introducing different copy numbers of the human FD ELP1 transgene into the Elp1 knockout mouse (Elp1−/−) and observed that human ELP1 expression rescues embryonic development in a dose-dependent manner. We then conducted a comprehensive transcriptome analysis in mouse embryos to identify genes and pathways whose expression correlates with the amount of ELP1. We found that ELP1 is essential for the expression of genes responsible for nervous system development. Further, gene length analysis of the differentially expressed genes showed that the loss of Elp1 mainly impacts the expression of long genes and that by gradually restoring Elongator, their expression is progressively rescued. Finally, through evaluation of co-expression modules, we identified gene sets with unique expression patterns that depended on ELP1 expression.",

keywords = "Elongator, ELP1, Familial dysautonomia, Neurodevelopmental disease, Transcriptional elongation",

author = "Elisabetta Morini and Dadi Gao and Logan, {Emily M.} and Monica Salani and Krauson, {Aram J.} and Anil Chekuri and Chen, {Yei Tsung} and Ashok Ragavendran and Probir Chakravarty and Serkan Erdin and Alexei Stortchevoi and Svejstrup, {Jesper Q.} and Talkowski, {Michael E.} and Slaugenhaupt, {Susan A.}",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2022",

doi = "10.1016/j.jgg.2021.11.011",

language = "English",

volume = "49",

pages = "654--665",

journal = "Journal of Genetics and Genomics",

issn = "1673-8527",

publisher = "Elsevier",

number = "7",

}

RIS

TY - JOUR

T1 - Developmental regulation of neuronal gene expression by Elongator complex protein 1 dosage

AU - Morini, Elisabetta

AU - Gao, Dadi

AU - Logan, Emily M.

AU - Salani, Monica

AU - Krauson, Aram J.

AU - Chekuri, Anil

AU - Chen, Yei Tsung

AU - Ragavendran, Ashok

AU - Chakravarty, Probir

AU - Erdin, Serkan

AU - Stortchevoi, Alexei

AU - Svejstrup, Jesper Q.

AU - Talkowski, Michael E.

AU - Slaugenhaupt, Susan A.

PY - 2022

Y1 - 2022

N2 - Familial dysautonomia (FD), a hereditary sensory and autonomic neuropathy, is caused by a mutation in the Elongator complex protein 1 (ELP1) gene that leads to a tissue-specific reduction of ELP1 protein. Our work to generate a phenotypic mouse model for FD headed to the discovery that homozygous deletion of the mouse Elp1 gene leads to embryonic lethality prior to mid-gestation. Given that FD is caused by a reduction, not loss, of ELP1, we generated two new mouse models by introducing different copy numbers of the human FD ELP1 transgene into the Elp1 knockout mouse (Elp1−/−) and observed that human ELP1 expression rescues embryonic development in a dose-dependent manner. We then conducted a comprehensive transcriptome analysis in mouse embryos to identify genes and pathways whose expression correlates with the amount of ELP1. We found that ELP1 is essential for the expression of genes responsible for nervous system development. Further, gene length analysis of the differentially expressed genes showed that the loss of Elp1 mainly impacts the expression of long genes and that by gradually restoring Elongator, their expression is progressively rescued. Finally, through evaluation of co-expression modules, we identified gene sets with unique expression patterns that depended on ELP1 expression.

AB - Familial dysautonomia (FD), a hereditary sensory and autonomic neuropathy, is caused by a mutation in the Elongator complex protein 1 (ELP1) gene that leads to a tissue-specific reduction of ELP1 protein. Our work to generate a phenotypic mouse model for FD headed to the discovery that homozygous deletion of the mouse Elp1 gene leads to embryonic lethality prior to mid-gestation. Given that FD is caused by a reduction, not loss, of ELP1, we generated two new mouse models by introducing different copy numbers of the human FD ELP1 transgene into the Elp1 knockout mouse (Elp1−/−) and observed that human ELP1 expression rescues embryonic development in a dose-dependent manner. We then conducted a comprehensive transcriptome analysis in mouse embryos to identify genes and pathways whose expression correlates with the amount of ELP1. We found that ELP1 is essential for the expression of genes responsible for nervous system development. Further, gene length analysis of the differentially expressed genes showed that the loss of Elp1 mainly impacts the expression of long genes and that by gradually restoring Elongator, their expression is progressively rescued. Finally, through evaluation of co-expression modules, we identified gene sets with unique expression patterns that depended on ELP1 expression.

KW - Elongator

KW - ELP1

KW - Familial dysautonomia

KW - Neurodevelopmental disease

KW - Transcriptional elongation

U2 - 10.1016/j.jgg.2021.11.011

DO - 10.1016/j.jgg.2021.11.011

M3 - Journal article

C2 - 34896608

AN - SCOPUS:85126017304

VL - 49

SP - 654

EP - 665

JO - Journal of Genetics and Genomics

JF - Journal of Genetics and Genomics

SN - 1673-8527

IS - 7

ER -

ID: 306900451