PXD036655

PXD036655 is an original dataset announced via ProteomeXchange.

Title	Beta cell dysfunction and dedifferentiation induced by Bone Morphogenetic Protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding
Description	Insufficient insulin secretion is a hallmark of type 2 diabetes and has been attributed to beta cell identity loss characterized by a decreased expression of several key beta cell genes. The pro-inflammatory factor BMP-2 is upregulated in islets of Langerhans from diabetic individuals and acts as an inhibitor of beta cell function and proliferation. Exposure to BMP-2 induces expression of Id1-4, Hes-1 and Hey-1, transcriptional regulators associated with loss of differentiation. The aim of this study was to investigate the mechanism of BMP-2 induced beta cell dysfunction and identity loss. Mouse islets exposed to BMP-2 for 10 days showed impaired insulin secretion and beta cell proliferation. BMP-2-induced beta cell dysfunction was associated with decreased expression of beta cell specific identity and proliferation markers such as Ins1, Ucn3 and Ki67 but increased expression of Id1-4, Hes-1 and Hey-1. BMP-2 regulated mRNA expression significantly correlated with corresponding protein expression. BMP-2 induced gene expression changes were associated with a predominant reduction in the H3K27ac mark and a decrease in NeuroD1 chromatin binding activity. These results show that BMP-2-induced beta cell dysfunction is associated with epigenetic changes, predominantly a reduction in H3K27ac and a decrease in NeuroD1 DNA binding resulting in altered beta cell gene expression.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:02:59.359.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martin R. Larsen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-12 06:20:40	ID requested
1	2023-07-20 11:12:12	announced
⏵ 2	2023-11-14 09:03:07	announced	2023-11-14: Updated project metadata.

Urizar AI, Prause M, Ingerslev LR, Wortham M, Sui Y, Sander M, Williams K, Barr, è, s R, Larsen MR, Christensen GL, Billestrup N, Beta cell dysfunction induced by bone morphogenetic protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding. Cell Death Dis, 14(7):399(2023) [pubmed]

submitter keyword: RNA, Histone,BMP-2, Proteomics

Nils Billestrup
contact affiliation	Department of Biomedical Science, University of Copenhagen, Denmark
contact email	billestrup@sund.ku.dk
lab head
Martin R. Larsen
contact affiliation	University of Southern Denmark
contact email	mrl@bmb.sdu.dk
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/2023/07/PXD036655

PRIDE project URI

• PRIDE
  1. PXD036655
     1. Label: PRIDE project
     2. Name: Beta cell dysfunction and dedifferentiation induced by Bone Morphogenetic Protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding