PXD008078-1

PXD008078 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2017-10-31 02:14:53	ID requested
⏵ 1	2018-01-08 07:01:00	announced

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]

curator keyword: Biological

submitter keyword: Nudt21 TMT

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

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PRIDE project URI

• PRIDE
  1. PXD008078
     1. Label: PRIDE project
     2. Name: Nudt21 controls cell fate by connecting alternative polyadenylation to chromatin signaling