PXD016586

PXD016586 is an original dataset announced via ProteomeXchange.

Title	High mobility group protein-mediated transcription requires DNA damage marker γ-H2AX
Description	The eukaryotic genome is organized into chromatins, the physiological template for DNA-dependent processes including replication, recombination, repair, and transcription. Chromatin-mediated transcription regulation involves DNA methylation, chromatin remodeling, and histone modifications. However, chromatin also contains non-histone chromatin-associated proteins, of which the high-mobility group (HMG) proteins are the most abundant. Although it is known that HMG proteins induce structural changes of chromatin, the processes underlying transcription regulation by HMG proteins are poorly understood. Here we decipher the molecular mechanism of transcription regulation mediated by the HMG AT-hook 2 protein (HMGA2). We combined proteomic, ChIP-seq, and transcriptome data to show that HMGA2-induced transcription requires phosphorylation of the histone variant H2AX at S139 (H2AXS139ph; γ-H2AX) mediated by the protein kinase ataxia telangiectasia mutated (ATM). Furthermore, we demonstrate the biological relevance of this mechanism within the context of TGFβ1 signaling. The interplay between HMGA2, ATM, and H2AX is a novel mechanism of transcription initiation. Our results link H2AXS139ph to transcription, assigning a new function for this DNA damage marker. Controlled chromatin opening during transcription may involve intermediates with DNA breaks that may require mechanisms that ensure the integrity of the genome.
HostingRepository	PRIDE
AnnounceDate	2020-12-15
AnnouncementXML	Submission_2021-04-06_02:15:33.888.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Guillermo Barreto
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-04 03:54:31	ID requested
1	2020-12-15 00:06:37	announced
⏵ 2	2021-04-06 02:15:34	announced	2021-04-06: Updated publication reference for PubMed record(s): 33594057.

Dobersch S, Rubio K, Singh I, G, ü, nther S, Graumann J, Cordero J, Castillo-Negrete R, Huynh MB, Mehta A, Braubach P, Cabrera-Fuentes H, Bernhagen J, Chao CM, Bellusci S, G, ü, nther A, Preissner KT, Kugel S, Dobreva G, Wygrecka M, Braun T, Papy-Garcia D, Barreto G, -H2AX precedes active DNA demethylation and transcription initiation. Nat Commun, 12(1):1072(2021) [pubmed]

curator keyword: Biological

submitter keyword: HMGA2, FACT, H2A.X, R-Loops, DNA demethylation, TGFB1

Guillermo Barreto
contact affiliation	Lung Cancer Epigenetics Research Group Max Planck Institute for Heart and Lung Research
contact email	guillermo.barreto@mpi-bn.mpg.de
lab head
Guillermo Barreto
contact affiliation	Max-Planck-Institute for Heart and Lung Research
contact email	guillermo.barreto@mpi-bn.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD016586
     1. Label: PRIDE project
     2. Name: High mobility group protein-mediated transcription requires DNA damage marker γ-H2AX