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Recent integrative epigenome analyses highlight the importance of functionally distinct chromatin states for accurate cell function. How these states are established and maintained is a matter of intense investigation. Here, we present evidence for DNA damage as an unexpected means to shape a protective chromatin environment at regions of recurrent replication stress (RS). Upon aberrant fork stalling, DNA damage signaling and concomitant H2AX phosphorylation coordinate the FACT-dependent deposition of macroH2A1.2, a histone variant that promotes DNA repair by homologous recombination (HR). MacroH2A1.2, in turn, facilitates the accumulation of the tumor suppressor and HR effector BRCA1 at replication forks to protect from RS-induced DNA damage. Consequently, replicating primary cells steadily accrue macroH2A1.2 at fragile regions, whereas macroH2A1.2 loss in these cells triggers DNA damage signaling-dependent senescence, a hallmark of RS. Altogether, our findings demonstrate that recurrent DNA damage contributes to the chromatin landscape to ensure the epigenomic integrity of dividing cells.
Pubmed ID: 29249653 RIS Download
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A powerful toolset for genome arithmetic allowing one to address common genomics tasks such as finding feature overlaps and computing coverage. Bedtools allows one to intersect, merge, count, complement, and shuffle genomic intervals from multiple files in widely-used genomic file formats such as BAM, BED, GFF/GTF, VCF. While each individual tool is designed to do a relatively simple task (e.g., intersect two interval files), quite sophisticated analyses can be conducted by combining multiple bedtools operations on the UNIX command line.
View all literature mentionsA generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms.
View all literature mentionsThis polyclonal targets FANCD2
View all literature mentionsThis monoclonal targets Replication Protein A
View all literature mentionsThis unknown targets Phospho-RPA32 (Ser4, Ser8)
View all literature mentionsThis unknown targets Phospho-RPA32 (Ser33)
View all literature mentionsThis polyclonal targets gamma H2A.X (phospho S139)
View all literature mentionsThis polyclonal targets goat anti-rabbit IgG-HRP
View all literature mentionsThis polyclonal targets Mouse IgG
View all literature mentionsThis polyclonal targets Chk2, phospho (Thr68)
View all literature mentionsThis monoclonal targets ATM, phospho (Ser1981)
View all literature mentionsThis monoclonal targets SSRP1
View all literature mentionsThis polyclonal targets Human Histone H2A - ChIP Grade
View all literature mentionsThis monoclonal targets Histone H2A
View all literature mentionsThis polyclonal targets SUPT16H
View all literature mentionsThis monoclonal targets GAPDH (6C5)
View all literature mentionsThis monoclonal targets PCNA (PC10)
View all literature mentionsThis monoclonal targets Human BRCA1
View all literature mentionsThis polyclonal secondary targets not applicable
View all literature mentionsThis monoclonal targets Histone H2B antibody [mAbcam 52484] - ChIP Grade
View all literature mentionsThis polyclonal targets Histone H2A.X antibody
View all literature mentionsThis monoclonal targets Histone H2A.X pSer139
View all literature mentionsThis polyclonal targets Histone Macro H2A.1
View all literature mentionsThis monoclonal targets Mouse macro-H2A1.2 Clone 14G7
View all literature mentionsCell line BJ [Human fibroblast] is a Finite cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Flp-In-T-REx-293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line IMR-90 is a Finite cell line with a species of origin Homo sapiens
View all literature mentionsCell line K-562 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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