PXD012146

PXD012146 is an original dataset announced via ProteomeXchange.

Title	Functions of the 12 different isoforms of the hepatocyte nuclear factor 4 alpha (HNF4α)
Description	HNF4α is a nuclear receptor regulating the transcription of genes involved mainly in development, cell differentiation and metabolism. Opposite functions for the two classes of P1 and P2 isoforms of HNF4α have recently been highlighted. These classes include 12 variants of HNF4α that can be expressed by the use of two promoters and by alternative splicing. Until now, the characterization of this transcription factor has ignored this diversity and has remained confined to the study of a fraction of the isoforms. We therefore wanted to clarify the situation by specifically characterizing the transcriptional functions of the 12 isoforms of HNF4α. We have generated for this purpose stable lines expressing each isoform of HNF4α in HCT 116 cells. We analyzed the whole transcriptome associated with each isoform by sequencing RNA, as well as their proteome by a BioID approach coupled to quantitative mass spectrometry. We noted major differences in the transcriptional function of the 12 isoforms. The α4, α5 and α6 isoforms have been characterized for the first time, and show a greatly reduced transcriptional potential. We have shown that these isoforms are unable to recognize the consensus response element of HNF4α. The α1 and α2 isoforms are the most potent regulators of gene expression, while the α3 isoform exhibits significantly reduced activity. Several transcription factors and coregulators have been identified as potential specific partners for certain HFH4α isoforms. The IRF-2BP2 co-repressor interacts specifically with isoforms which include the long form of the F domain of HNF4α. This specific interaction could explain the large number of genes modulated negatively by α1 and α2 compared to α3. The analysis integrating the vast amount of transcriptomic and proteomic data allows the identification of transcriptional regulatory mechanisms specific to certain isoforms, demonstrating the importance of considering all isoforms which can have diverse functions.
HostingRepository	PRIDE
AnnounceDate	2020-04-17
AnnouncementXML	Submission_2020-04-16_22:19:01.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Francois-Michel Boisvert
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue; 6x(13)C labeled residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-12-21 01:59:07	ID requested
⏵ 1	2020-04-16 22:19:02	announced

Lambert É, Babeu JP, Simoneau J, Raisch J, Lavergne L, L, é, vesque D, Jolibois É, Avino M, Scott MS, Boudreau F, Boisvert FM, Encodes Isoforms with Distinct Transcriptional Functions. Mol Cell Proteomics, 19(5):808-827(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: HNF4α, colorectal cancer, nuclear receptors, transcription, proteomics, SILAC, isoforms

Francois-Michel Boisvert
contact affiliation	Department of Anatomy and Cell Biology, Université de Sherbrooke, Canada
contact email	fm.boisvert@usherbrooke.ca
lab head
Francois-Michel Boisvert
contact affiliation	Université de Sherbrooke
contact email	fm.boisvert@usherbrooke.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012146
     1. Label: PRIDE project
     2. Name: Functions of the 12 different isoforms of the hepatocyte nuclear factor 4 alpha (HNF4α)