Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

P53 Chip-Seq in U2OS treated with UV

ABSTRACT: We report that TAF1 phosphorylates p53 at Thr55 on the p21 promoter and this phosphorylation leads to dissociation of p53 from the promoter. Indeed, ChIP-Seq analysis reveals p53 undergoes promoter dissociation at a global level after response to DNA damage, underscoring general nature of the regulation. UVC treatment at the time points indicated was used to access p53 transcription factor signal induction and termination.

INSTRUMENT(S): Illumina HiSeq 2000

ORGANISM(S): Homo sapiens

SUBMITTER: Selene Bobadilla

PROVIDER: E-MTAB-1988 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Phosphorylation of p53 by TAF1 inactivates p53-dependent transcription in the DNA damage response.

Wu Yong Y Lin Joy C JC Piluso Landon G LG Dhahbi Joseph M JM Bobadilla Selene S Spindler Stephen R SR Liu Xuan X

Molecular cell 20131127 1

While p53 activation has long been studied, the mechanisms by which its targets genes are restored to their preactivation state are less clear. We report here that TAF1 phosphorylates p53 at Thr55, leading to dissociation of p53 from the p21 promoter and inactivation of transcription late in the DNA damage response. We further show that cellular ATP level might act as a molecular switch for Thr55 phosphorylation on the p21 promoter, indicating that TAF1 is a cellular ATP sensor. Upon DNA damage, ...[more]

PMID: 24289924

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Project description:Studies of human embryonic stem cells (hESCs) commonly describe the non-functional p53-p21 axis of the G1/S checkpoint pathway with subsequent relevance for cell cycle regulation and the DNA damage response (DDR). Importantly, p21 mRNA is clearly present and upregulated after the DDR in hESCs but p21 protein is not detectable. In this article, we provide evidence that expression of p21 protein is directly regulated by the microRNA pathway under standard culture conditions and after DNA damage. The DDR in hESCs leads to upregulation of tens of microRNAs, including hESC-specific microRNAs such as those of the miR-302 family, miR-371-372 family, or C19MC microRNA cluster. Most importantly, we show that the hESC-enriched microRNA family miR-302 (miR-302a, miR-302b, miR-302c, and miR-302d) directly contributes to regulation of p21 expression in hESCs and thus demonstrate a novel function for miR-302s in hESCS. The described mechanism elucidates the role of microRNAs in regulation of important molecular pathway governing the G1/S transition checkpoint before as well as after DNA damage. Karyotypically normal hESC lines CCTL-14 (46, XX, at passages 20M-bM-^@M-^S30 and 242M-bM-^@M-^S250, respectively) was used in this study (for detailed characterization of hESC lines see International Stem Cell Registry: http://www.iscr-admin). For UVC irradiation, culture media were aspirated and cells were washed once with phosphate-buffered saline (PBS) without Mg2+ and Ca2+ (pH 7.4). For each time point, nine culture dishes were independently irradiated with a dose of 3 J/m2. Cells were then further incubated in culture media (37M-BM-0C/5% CO2) until they were harvested at 4, 8, and 16 hrs, respectively, post-UVC treatment. Differentiation and culture of NPCs derived from hESCs To induce neural differentiation, we utilized a protocol based on embryoid body (EB) formation with simultaneous all-trans-retinoic acid (RA) treatment. Colonies of hESCs were transferred to a non-adherent cell culture dish in the presence of differentiation media [DMEM/F12:Neurobasal 1:1, N2, B27 (Invitrogen), 2 mmol/l L-Glutamine (all media components from Invitrogen, Carlsbad, CA, USA), 1M-CM-^W MEM non-essential amino acids, 0.5% penicillin-streptomycin, 100 M-BM-5mol/l M-NM-2-2 mercaptoethanol (Sigma-Aldrich, St. Louis, MO, USA) and 20 ng/ml FGF-2 (PeproTech, Rocky Hill, NJ, USA)]. RA was added (Sigma-Aldrich, concentration 0.5 M-BM-5mol/l) into fresh differentiation media on days 6, 10, and 14 after the beginning of EB development. On day 16, cells were dissociated using Accutase (Sigma-Aldrich) and plated on a gelatin-coated cell culture dish in maintenance media (DMEM/F12, N2, B27, L-Glutamine, MEM non-essential amino acids, 0.5% penicillin-streptomycin, 100 M-BM-5mol/l M-NM-2-2 mercaptoethanol, and 20 ng/ml FGF-2). Cells were passaged twice and subsequently harvested for RNA isolation.

Dataset Information

P53 Chip-Seq in U2OS treated with UV

Publications

Phosphorylation of p53 by TAF1 inactivates p53-dependent transcription in the DNA damage response.

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