Integrative genome-wide analysis of dopaminergic neuron-specific PARIS expression in Drosophila dissects recognition of multiple PPAR-γ associated gene regulation

Abstract The transcriptional repressor called parkin interacting substrate (PARIS; ZNF746) was initially identified as a novel co-substrate of parkin and PINK1 that leads to Parkinson’s disease (PD) by disrupting mitochondrial biogenesis through peroxisome proliferator-activated receptor gamma (PPAR...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Volkan Yazar, Sung-Ung Kang, Shinwon Ha, Valina L. Dawson, Ted M. Dawson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b3049af49e7a40df8697aa04359b1412
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b3049af49e7a40df8697aa04359b1412
record_format	dspace
spelling	oai:doaj.org-article:b3049af49e7a40df8697aa04359b14122021-11-08T10:47:44ZIntegrative genome-wide analysis of dopaminergic neuron-specific PARIS expression in Drosophila dissects recognition of multiple PPAR-γ associated gene regulation10.1038/s41598-021-00858-72045-2322https://doaj.org/article/b3049af49e7a40df8697aa04359b14122021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00858-7https://doaj.org/toc/2045-2322Abstract The transcriptional repressor called parkin interacting substrate (PARIS; ZNF746) was initially identified as a novel co-substrate of parkin and PINK1 that leads to Parkinson’s disease (PD) by disrupting mitochondrial biogenesis through peroxisome proliferator-activated receptor gamma (PPARγ) coactivator -1α (PGC-1α) suppression. Since its initial discovery, growing evidence has linked PARIS to defective mitochondrial biogenesis observed in PD pathogenesis. Yet, dopaminergic (DA) neuron-specific mechanistic underpinnings and genome-wide PARIS binding landscape has not been explored. We employed conditional translating ribosome affinity purification (TRAP) followed by RNA sequencing (TRAP-seq) for transcriptome profiling of DA neurons in transgenic Drosophila lines expressing human PARIS wild type (WT) or mutant (C571A). We also generated genome-wide maps of PARIS occupancy using ChIP-seq in human SH-SY5Y cells. The results demonstrated that PPARγ functions as a master regulator of PARIS-induced molecular changes at the transcriptome level, confirming that PARIS acts primarily on PGC-1α to lead to neurodegeneration in PD. Moreover, we identified that PARIS actively modulates expression of PPARγ target genes by physically binding to the promoter regions. Together, our work revealed how PARIS drives adverse effects on modulation of PPAR-γ associated gene clusters in DA neurons.Volkan YazarSung-Ung KangShinwon HaValina L. DawsonTed M. DawsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Volkan Yazar Sung-Ung Kang Shinwon Ha Valina L. Dawson Ted M. Dawson Integrative genome-wide analysis of dopaminergic neuron-specific PARIS expression in Drosophila dissects recognition of multiple PPAR-γ associated gene regulation
description	Abstract The transcriptional repressor called parkin interacting substrate (PARIS; ZNF746) was initially identified as a novel co-substrate of parkin and PINK1 that leads to Parkinson’s disease (PD) by disrupting mitochondrial biogenesis through peroxisome proliferator-activated receptor gamma (PPARγ) coactivator -1α (PGC-1α) suppression. Since its initial discovery, growing evidence has linked PARIS to defective mitochondrial biogenesis observed in PD pathogenesis. Yet, dopaminergic (DA) neuron-specific mechanistic underpinnings and genome-wide PARIS binding landscape has not been explored. We employed conditional translating ribosome affinity purification (TRAP) followed by RNA sequencing (TRAP-seq) for transcriptome profiling of DA neurons in transgenic Drosophila lines expressing human PARIS wild type (WT) or mutant (C571A). We also generated genome-wide maps of PARIS occupancy using ChIP-seq in human SH-SY5Y cells. The results demonstrated that PPARγ functions as a master regulator of PARIS-induced molecular changes at the transcriptome level, confirming that PARIS acts primarily on PGC-1α to lead to neurodegeneration in PD. Moreover, we identified that PARIS actively modulates expression of PPARγ target genes by physically binding to the promoter regions. Together, our work revealed how PARIS drives adverse effects on modulation of PPAR-γ associated gene clusters in DA neurons.
format	article
author	Volkan Yazar Sung-Ung Kang Shinwon Ha Valina L. Dawson Ted M. Dawson
author_facet	Volkan Yazar Sung-Ung Kang Shinwon Ha Valina L. Dawson Ted M. Dawson
author_sort	Volkan Yazar
title	Integrative genome-wide analysis of dopaminergic neuron-specific PARIS expression in Drosophila dissects recognition of multiple PPAR-γ associated gene regulation
title_short	Integrative genome-wide analysis of dopaminergic neuron-specific PARIS expression in Drosophila dissects recognition of multiple PPAR-γ associated gene regulation
title_full	Integrative genome-wide analysis of dopaminergic neuron-specific PARIS expression in Drosophila dissects recognition of multiple PPAR-γ associated gene regulation
title_fullStr	Integrative genome-wide analysis of dopaminergic neuron-specific PARIS expression in Drosophila dissects recognition of multiple PPAR-γ associated gene regulation
title_full_unstemmed	Integrative genome-wide analysis of dopaminergic neuron-specific PARIS expression in Drosophila dissects recognition of multiple PPAR-γ associated gene regulation
title_sort	integrative genome-wide analysis of dopaminergic neuron-specific paris expression in drosophila dissects recognition of multiple ppar-γ associated gene regulation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b3049af49e7a40df8697aa04359b1412
work_keys_str_mv	AT volkanyazar integrativegenomewideanalysisofdopaminergicneuronspecificparisexpressionindrosophiladissectsrecognitionofmultipleppargassociatedgeneregulation AT sungungkang integrativegenomewideanalysisofdopaminergicneuronspecificparisexpressionindrosophiladissectsrecognitionofmultipleppargassociatedgeneregulation AT shinwonha integrativegenomewideanalysisofdopaminergicneuronspecificparisexpressionindrosophiladissectsrecognitionofmultipleppargassociatedgeneregulation AT valinaldawson integrativegenomewideanalysisofdopaminergicneuronspecificparisexpressionindrosophiladissectsrecognitionofmultipleppargassociatedgeneregulation AT tedmdawson integrativegenomewideanalysisofdopaminergicneuronspecificparisexpressionindrosophiladissectsrecognitionofmultipleppargassociatedgeneregulation
_version_	1718442653987635200

Integrative genome-wide analysis of dopaminergic neuron-specific PARIS expression in Drosophila dissects recognition of multiple PPAR-γ associated gene regulation

Ejemplares similares