Dataset Information

High mobility group protein-mediated transcription requires DNA damage marker γ-H2AX

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryonic Fibroblast

SUBMITTER: Guillermo Barreto

LAB HEAD: Guillermo Barreto

PROVIDER: PXD016586 | Pride | 2020-12-15

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	20190405_SJ_HF_LC1200_StefanieDobersch_Sucrose_TMT_01.raw	Raw
	20190405_SJ_HF_LC1200_StefanieDobersch_Sucrose_TMT_02.raw	Raw
	20190405_SJ_HF_LC1200_StefanieDobersch_Sucrose_TMT_03.raw	Raw
	20190405_SJ_HF_LC1200_StefanieDobersch_Sucrose_TMT_04.raw	Raw
	20190405_SJ_HF_LC1200_StefanieDobersch_Sucrose_TMT_05.raw	Raw

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Publications

Positioning of nucleosomes containing γ-H2AX precedes active DNA demethylation and transcription initiation.

Dobersch Stephanie S Rubio Karla K Singh Indrabahadur I Günther Stefan S Graumann Johannes J Cordero Julio J Castillo-Negrete Rafael R Huynh Minh Bao MB Mehta Aditi A Braubach Peter P Cabrera-Fuentes Hector H Bernhagen Jürgen J Chao Cho-Ming CM Bellusci Saverio S Günther Andreas A Preissner Klaus T KT Kugel Sita S Dobreva Gergana G Wygrecka Malgorzata M Braun Thomas T Papy-Garcia Dulce D Barreto Guillermo G

Nature communications 20210216 1

In addition to nucleosomes, chromatin contains non-histone chromatin-associated proteins, of which the high-mobility group proteins are the most abundant. Chromatin-mediated regulation of transcription involves DNA methylation and histone modifications. However, the order of events and the precise function of high-mobility group proteins during transcription initiation remain unclear. Here we show that high-mobility group AT-hook 2 protein (HMGA2) induces DNA nicks at the transcription start sit ...[more]

PMID: 33594057

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