PXD025739

PXD025739 is an original dataset announced via ProteomeXchange.

Title	CHD8 Suppression Impacts on Histone H3 Lysine 36 Trimethylation and Alters RNA Alternative Splicing
Description	Disruptive mutations in the chromodomain helicase DNA binding protein 8 (CHD8) have been recurrently associated with Autism Spectrum Disorders (ASD). Here we investigated how chromatin reacts to CHD8 suppression by analyzing a panel of histone modifications in induced pluripotent stem cell-derived neural progenitors. CHD8 suppression led to significant reduction (47.82%) in histone H3K36me3 peaks at gene bodies, particularly impacting on transcriptional elongation chromatin states. H3K36me3 reduction specifically affects highly expressed, CHD8-bound genes and correlates with altered alternative splicing patterns of 408 genes implicated in “regulation of RNA splicing”, “mRNA catabolic process”. Interestingly, mass-spectrometry analysis uncovered a novel interaction between CHD8 and the splicing regulator Heterogeneous Nuclear Ribonucleoprotein L (hnRNPL), providing the first mechanistic insights to explain CHD8-suppression splicing phenotype, partially implicating SETD2, H3K36me3 methyltransferase. In summary, our results point toward broad molecular consequences of CHD8 suppression, entailing altered histone deposition/maintenance and RNA processing regulation as important regulatory processes in ASD.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:37:03.788.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Romina Belli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-30 04:58:08	ID requested
1	2023-03-10 20:32:08	announced
⏵ 2	2023-11-14 08:37:04	announced	2023-11-14: Updated project metadata.

Kerschbamer E, Arnoldi M, Tripathi T, Pellegrini M, Maturi S, Erdin S, Salviato E, Di Leva F, Sebesty, é, n E, Dassi E, Zarantonello G, Benelli M, Campos E, Basson MA, Gusella JF, Gustincich S, Piazza S, Demichelis F, Talkowski ME, Ferrari F, Biagioli M, CHD8 suppression impacts on histone H3 lysine 36 trimethylation and alters RNA alternative splicing. Nucleic Acids Res, 50(22):12809-12828(2022) [pubmed]

submitter keyword: Autism Spectrum Disorder, CHD8, Alternative Splicing, Chromatin, H3K36me3

Marta Biagioli
contact affiliation	NeuroEpigenetics Lab - Department of Cellular, Computational and Integrative Biology - CIBIO University of Trento, Via Sommarive 9, I - 38123 Povo (Trento)
contact email	marta.biagioli@unitn.it
lab head
Romina Belli
contact affiliation	University of Trento
contact email	romina.belli@unitn.it
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/PXD025739

PRIDE project URI

• PRIDE
  1. PXD025739
     1. Label: PRIDE project
     2. Name: CHD8 Suppression Impacts on Histone H3 Lysine 36 Trimethylation and Alters RNA Alternative Splicing