PXD008078 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Nudt21 controls cell fate by connecting alternative polyadenylation to chromatin signaling |
Description | Cell fate transitions involve rapid changes of gene expression patterns and global chromatin remodeling, yet the underlying regulatory pathways remain incompletely understood. Here, we used transcription-factor induced reprogramming of somatic cells into pluripotent cells to screen for novel regulators of cell fate change. We identified the RNA processing factor Nudt21, a component of the pre-mRNA cleavage and polyadenylation complex, as a potent barrier to reprogramming. Importantly, suppression of Nudt21 not only enhanced the generation of induced pluripotent stem cells but also facilitated the conversion of fibroblasts into trophoblast stem cells and delayed the differentiation of myeloid precursor cells into macrophages, suggesting a broader role for Nudt21 in restricting cell fate change. Polyadenylation site sequencing (PAS-seq) revealed that Nudt21 directs differential polyadenylation of over 1,500 transcripts in cells acquiring pluripotency. While only a fraction of these transcripts changed expression at the protein level, this fraction was strongly enriched for chromatin regulators, including components of the PAF, polycomb, and trithorax complexes. Co-suppression analysis further suggests that these chromatin factors are largely responsible for Nudt21’s effect on reprogramming, providing a mechanistic basis for our observations. Collectively, our data uncover Nudt21 as a novel post-transcriptional regulator of mammalian cell fate and establish a direct, previously unappreciated link between alternative polyadenylation and chromatin signaling. |
HostingRepository | PRIDE |
AnnounceDate | 2018-01-08 |
AnnouncementXML | Submission_2018-01-08_07:00:58.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Marian Kalocsay |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2017-10-31 02:14:53 | ID requested | |
⏵ 1 | 2018-01-08 07:01:00 | announced | |
Publication List
Brumbaugh J, Di Stefano B, Wang X, Borkent M, Forouzmand E, Clowers KJ, Ji F, Schwarz BA, Kalocsay M, Elledge SJ, Chen Y, Sadreyev RI, Gygi SP, Hu G, Shi Y, Hochedlinger K, Nudt21 Controls Cell Fate by Connecting Alternative Polyadenylation to Chromatin Signaling. Cell, 172(1-2):106-120.e21(2018) [pubmed] |
Keyword List
curator keyword: Biological |
submitter keyword: Nudt21 TMT |
Contact List
Konrad Hochedlinger |
contact affiliation | Harvard Department of Stem Cell and Regenerative Biology Cambridge, MA 02138, USA |
contact email | khochedlinger@helix.mgh.harvard.edu |
lab head | |
Marian Kalocsay |
contact affiliation | Harvard Medical School |
contact email | marian_kalocsay@hms.harvard.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD008078
- Label: PRIDE project
- Name: Nudt21 controls cell fate by connecting alternative polyadenylation to chromatin signaling