PXD008053

PXD008053 is an original dataset announced via ProteomeXchange.

Title	Mice Hippocampus neuron HT22 LC-MS
Description	Ketone 3-hydroxybutyrate (3OHB) has been proved to be a neuroprotective endogenous molecule in multiple neurodegenerative diseases, but the detailed mechanisms of action has not been fully uncovered. Here, we employed a quantitative proteomics approach to assess the global protein expression pattern of neuron cells which were incorporated with 3OHB. While 3OHB did not derive dramatic proteome pattern fluctuation in HT22 cells, a big portion of the proteome alteration are found to be 3OHB specific responses (including: cell metabolism, protein acetylation, cognition, neurodegeneration diseases). Combining with disease related protein-protein interaction network analysis, we successfully pinpointed a hub marker, Histone lysine 27 trimethylation (H3K27me3), which has been widely studied in multiple neurodegenerative diseases, but still hasn’t been connected to 3OHB derived neuroprotective effects yet. In addition, our data suggested that the co-occurrence of H3K4me3 and H3K27me3 which was defined as chromatin bivalency referring “poised” transcriptional state could be perturbed by 3OHB, since both H3K4me3 and H3K27me3 were showing sensitive response to 3OHB. Integrative transcriptomics and epigenomics analysis highlighted bivalent transcription factors may play critical roles in 3OHB derived disease protection and alteration of neuronal development processes. To further validate and explore the possible scenario, we performed transcriptomics profiling of 3OHB perturbation upon neural differentiation process. The gene set enrichment analysis has shown that 3OHB could impair the fate decision of neural precursor cells by repressing and promoting their differentiation and proliferation related biological processes, respectively. Another interesting phenomenon is that two of relative high abundant Histone lysine hydroxybutyrylation sites (H2AK118bhb, H2BK34bhb) also responded to 3OHB fulguration. Those two sites are happen to be the most important monoubiquitylation sites that play critical role in regulating of H3K27 methylation and H3K4 (and K79) methylation, respectively. One may speculate that H2AK118bhb and H2BK34bhb involve in or even derive chromatin bivalency alteration upon 3OHB perturbation in neural systems.Taking together, our study provides a novel scenario for deciphering the 3OHB and its mechanisms of action in neural systems both in neurodegeneration disease pathogenesis and neural development process.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:01:38.245.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xinliang ZHU
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-10-26 04:35:52	ID requested
1	2023-03-10 15:17:57	announced
⏵ 2	2023-11-14 08:01:39	announced	2023-11-14: Updated project metadata.

Zhu XL, Du H, Wang LL, Hu EL, Li N, Lu HX, Chen GQ, Lu XY, Integrative Proteome Analysis Revels 3-Hydroxybutyrate Exerts Neuroprotective Effect by Influencing Chromatin Bivalency. Int J Mol Sci, 24(1):(2023) [pubmed]

curator keyword: Biological

submitter keyword: neuron, central nervous system, proteomics, bivalent chromatin, Histone lysine hydroxybutyrylation, HT22, beta-hydroxybutyrate,Mice, transcriptomics

Xiao yun LU
contact affiliation	Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, Shaanxi Province, China.
contact email	luxy05@126.com
lab head
Xinliang ZHU
contact affiliation	Hong Kong University of science and technology
contact email	xzhuaf@connect.ust.hk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/03/PXD008053

PRIDE project URI

• PRIDE
  1. PXD008053
     1. Label: PRIDE project
     2. Name: Mice Hippocampus neuron HT22 LC-MS