PXD008648

PXD008648 is an original dataset announced via ProteomeXchange.

Title	Activation of neuronal genes via LINE-1 elements upon global DNA demethylation in human neural progenitors
Description	DNA methylation is an important epigenetic modification that is thought to contribute to the maintenance of genomic integrity in somatic cells, in part through the silencing of transposable elements (TEs). In this study we used CRISPR/Cas9 mediated gene editing to disrupt DNMT1, the key maintenance methyltransferase in somatic human cells. Surprisingly, and in contrast to findings in mouse, inactivation of DNMT1 in human neural progenitor cells (hNPCs) resulted in viable proliferating cells that maintained the expression of appropriate marker genes. Removal of DNA methylation in hNPCs resulted in a specific activation of hominid-specific LINE-1 elements (L1s), while other classes of TEs remained silent. We also found that the transcriptionally activated L1s acted as alternative promoters for many protein-coding genes involved in neuronal functions, uncovering an L1-based transcriptional network influencing neuronal protein-coding genes. Our results prove novel mechanistic insight into the role of DNA methylation in somatic human cells.
HostingRepository	PRIDE
AnnounceDate	2019-05-30
AnnouncementXML	Submission_2019-07-23_06:29:49.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jenny Hansson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	4x(2)H labeled dimethylated residue; dimethylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2018-01-10 03:49:00	ID requested
1	2019-05-29 19:01:49	announced
⏵ 2	2019-07-23 06:29:50	announced	Updated publication reference for PubMed record(s): 31320637.

J, ö, nsson ME, Ludvik Bratt, å, s P, Gustafsson C, Petri R, Yudovich D, Pircs K, Verschuere S, Madsen S, Hansson J, Larsson J, M, å, nsson R, Meissner A, Jakobsson J, Activation of neuronal genes via LINE-1 elements upon global DNA demethylation in human neural progenitors. Nat Commun, 10(1):3182(2019) [pubmed]

curator keyword: Biological

submitter keyword: Human, DNMT1, LC-MSMS

Jenny Hansson
contact affiliation	Lund Stem Cell Center, Division of Molecular Hematology, Lund University, Lund, Sweden
contact email	jenny.hansson@med.lu.se
lab head
Jenny Hansson
contact affiliation	Lund University
contact email	jehansson@gmail.com
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/2019/05/PXD008648

PRIDE project URI

• PRIDE
  1. PXD008648
     1. Label: PRIDE project
     2. Name: Activation of neuronal genes via LINE-1 elements upon global DNA demethylation in human neural progenitors