A cross-species approach to identify transcriptional regulators exemplified for Dnajc22 and Hnf4a

Abstract There is an enormous need to make better use of the ever increasing wealth of publicly available genomic information and to utilize the tremendous progress in computational approaches in the life sciences. Transcriptional regulation of protein-coding genes is a major mechanism of controllin...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	A. C. Aschenbrenner, K. Bassler, M. Brondolin, L. Bonaguro, P. Carrera, K. Klee, T. Ulas, J. L. Schultze, M. Hoch
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f2786cb37a584a7dbecb5be727dda15f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f2786cb37a584a7dbecb5be727dda15f
record_format	dspace
spelling	oai:doaj.org-article:f2786cb37a584a7dbecb5be727dda15f2021-12-02T15:06:20ZA cross-species approach to identify transcriptional regulators exemplified for Dnajc22 and Hnf4a10.1038/s41598-017-04370-92045-2322https://doaj.org/article/f2786cb37a584a7dbecb5be727dda15f2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04370-9https://doaj.org/toc/2045-2322Abstract There is an enormous need to make better use of the ever increasing wealth of publicly available genomic information and to utilize the tremendous progress in computational approaches in the life sciences. Transcriptional regulation of protein-coding genes is a major mechanism of controlling cellular functions. However, the myriad of transcription factors potentially controlling transcription of any given gene makes it often difficult to quickly identify the biological relevant transcription factors. Here, we report on the identification of Hnf4a as a major transcription factor of the so far unstudied DnaJ heat shock protein family (Hsp40) member C22 (Dnajc22). We propose an approach utilizing recent advances in computational biology and the wealth of publicly available genomic information guiding the identification of potential transcription factor candidates together with wet-lab experiments validating computational models. More specifically, the combined use of co-expression analyses based on self-organizing maps with sequence-based transcription factor binding prediction led to the identification of Hnf4a as the potential transcriptional regulator for Dnajc22 which was further corroborated using publicly available datasets on Hnf4a. Following this procedure, we determined its functional binding site in the murine Dnajc22 locus using ChIP-qPCR and luciferase assays and verified this regulatory loop in fruitfly, zebrafish, and humans.A. C. AschenbrennerK. BasslerM. BrondolinL. BonaguroP. CarreraK. KleeT. UlasJ. L. SchultzeM. HochNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q A. C. Aschenbrenner K. Bassler M. Brondolin L. Bonaguro P. Carrera K. Klee T. Ulas J. L. Schultze M. Hoch A cross-species approach to identify transcriptional regulators exemplified for Dnajc22 and Hnf4a
description	Abstract There is an enormous need to make better use of the ever increasing wealth of publicly available genomic information and to utilize the tremendous progress in computational approaches in the life sciences. Transcriptional regulation of protein-coding genes is a major mechanism of controlling cellular functions. However, the myriad of transcription factors potentially controlling transcription of any given gene makes it often difficult to quickly identify the biological relevant transcription factors. Here, we report on the identification of Hnf4a as a major transcription factor of the so far unstudied DnaJ heat shock protein family (Hsp40) member C22 (Dnajc22). We propose an approach utilizing recent advances in computational biology and the wealth of publicly available genomic information guiding the identification of potential transcription factor candidates together with wet-lab experiments validating computational models. More specifically, the combined use of co-expression analyses based on self-organizing maps with sequence-based transcription factor binding prediction led to the identification of Hnf4a as the potential transcriptional regulator for Dnajc22 which was further corroborated using publicly available datasets on Hnf4a. Following this procedure, we determined its functional binding site in the murine Dnajc22 locus using ChIP-qPCR and luciferase assays and verified this regulatory loop in fruitfly, zebrafish, and humans.
format	article
author	A. C. Aschenbrenner K. Bassler M. Brondolin L. Bonaguro P. Carrera K. Klee T. Ulas J. L. Schultze M. Hoch
author_facet	A. C. Aschenbrenner K. Bassler M. Brondolin L. Bonaguro P. Carrera K. Klee T. Ulas J. L. Schultze M. Hoch
author_sort	A. C. Aschenbrenner
title	A cross-species approach to identify transcriptional regulators exemplified for Dnajc22 and Hnf4a
title_short	A cross-species approach to identify transcriptional regulators exemplified for Dnajc22 and Hnf4a
title_full	A cross-species approach to identify transcriptional regulators exemplified for Dnajc22 and Hnf4a
title_fullStr	A cross-species approach to identify transcriptional regulators exemplified for Dnajc22 and Hnf4a
title_full_unstemmed	A cross-species approach to identify transcriptional regulators exemplified for Dnajc22 and Hnf4a
title_sort	cross-species approach to identify transcriptional regulators exemplified for dnajc22 and hnf4a
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f2786cb37a584a7dbecb5be727dda15f
work_keys_str_mv	AT acaschenbrenner acrossspeciesapproachtoidentifytranscriptionalregulatorsexemplifiedfordnajc22andhnf4a AT kbassler acrossspeciesapproachtoidentifytranscriptionalregulatorsexemplifiedfordnajc22andhnf4a AT mbrondolin acrossspeciesapproachtoidentifytranscriptionalregulatorsexemplifiedfordnajc22andhnf4a AT lbonaguro acrossspeciesapproachtoidentifytranscriptionalregulatorsexemplifiedfordnajc22andhnf4a AT pcarrera acrossspeciesapproachtoidentifytranscriptionalregulatorsexemplifiedfordnajc22andhnf4a AT kklee acrossspeciesapproachtoidentifytranscriptionalregulatorsexemplifiedfordnajc22andhnf4a AT tulas acrossspeciesapproachtoidentifytranscriptionalregulatorsexemplifiedfordnajc22andhnf4a AT jlschultze acrossspeciesapproachtoidentifytranscriptionalregulatorsexemplifiedfordnajc22andhnf4a AT mhoch acrossspeciesapproachtoidentifytranscriptionalregulatorsexemplifiedfordnajc22andhnf4a AT acaschenbrenner crossspeciesapproachtoidentifytranscriptionalregulatorsexemplifiedfordnajc22andhnf4a AT kbassler crossspeciesapproachtoidentifytranscriptionalregulatorsexemplifiedfordnajc22andhnf4a AT mbrondolin crossspeciesapproachtoidentifytranscriptionalregulatorsexemplifiedfordnajc22andhnf4a AT lbonaguro crossspeciesapproachtoidentifytranscriptionalregulatorsexemplifiedfordnajc22andhnf4a AT pcarrera crossspeciesapproachtoidentifytranscriptionalregulatorsexemplifiedfordnajc22andhnf4a AT kklee crossspeciesapproachtoidentifytranscriptionalregulatorsexemplifiedfordnajc22andhnf4a AT tulas crossspeciesapproachtoidentifytranscriptionalregulatorsexemplifiedfordnajc22andhnf4a AT jlschultze crossspeciesapproachtoidentifytranscriptionalregulatorsexemplifiedfordnajc22andhnf4a AT mhoch crossspeciesapproachtoidentifytranscriptionalregulatorsexemplifiedfordnajc22andhnf4a
_version_	1718388554369859584

A cross-species approach to identify transcriptional regulators exemplified for Dnajc22 and Hnf4a

Ejemplares similares