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Series GSE42306 Query DataSets for GSE42306
Status Public on Sep 07, 2014
Title H2A.X native ChIP-Seq in ESC and iPSC: Histone Variant H2A.X Mediated Epigenetic Mechanisms are Critical for Maintaining Genome Stability and Pluripotency in ES and iPS Cells
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary It is well-known that embryonic stem cells (ESC) are much more sensitive to replication-induced stress than differentiated cells but the underpinning mechanisms are largely unknown. H2A.X, a minor variant of H2A, constitutes only 1-10% of the mammalian genome. H2A.X plays a well-known for role in the DNA damage response and maintaining stability in the genome, including the regions frequently experiencing replication stress, such as the fragile sites. Intriguingly, several recent studies have reported that H2A.X function is elevated in ESC; and others reported that H2A.X function is provoked during cellular reprogramming (in induced pluripotent stem cells, iPSC), indicating that increased proliferation during iPS may trigger replication stress and the H2A.X DNA damage response. However, several studies of genomic instability in iPSC led to different conclusions on this important issue. For example, frequent copy number variants (CNV) were reported at the genomic regions sensitive to replication stress, such as the fragile sites. On the other hand, another study reported the lack of genomic instability in mouse iPS clones that are able to generate “all-iPS” animals in tetraploid complementation assays (4N+ iPSC), indicative of a potential link between pluripotency and genome integrity. However, whether if high level genomic instability occurs in the 4N- iPSC iPSC clones at replication stress sensitive regions is unknown. Moreover, due to the lack of mechanistic insights on genome integrity maintenance, how pluripotency and genome integrity are connected remains elusive. Here we show that H2A.X plays unexpected roles in maintaining pluripotency and genome integrity in ESC and iPSC. In ESC, it is specially enriched at genomic regions sensitive to replication stress so that it protects genome integrity thereat. Faithful H2A.X deposition is critical for genome integrity and pluripotency in iPSC. H2A.X depositions in 4N+ iPSC clones faithfully recapitulate the ESC pattern and therefore, prevent genome instability. On the other hand, insufficient H2A.X depositions in 4N- iPSC clones at such regions lead to genome instability and defects in replication stress response and DNA repair, reminiscent of the H2A.X deficient ESC.
Overall design Detect and compare different H2A.X deposition patterns in ES cells and iPS cells, with Illumina HiSeq 2000 and Illumina Genome Analyzer IIx
Contributor(s) Wu T, Xiao A
Citation(s) 25192463
Submission date Nov 15, 2012
Last update date May 15, 2019
Contact name Andrew Zhuo Xiao
Phone 203-785-5111
Organization name Yale Stem Cell Center
Department Genetics
Lab Andrew Xiao
Street address 10 Amistad St
City New Haven
State/province CT
ZIP/Postal code 06519
Country USA
Platforms (2)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (33)
GSM1037471 H2AX_iPSC_4N_positive_PF1
GSM1037472 H2AX_iPSC_4N_positive_TTF1
GSM1037473 H2AX_iPSC_4N_positive_Bcell1
This SubSeries is part of SuperSeries:
GSE42309 H2A.X function in mouse ESC and iPSC (ChIPSeq and CNVs)
BioProject PRJNA181007
SRA SRP017189

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Supplementary file Size Download File type/resource
GSE42306_RAW.tar 5.8 Gb (http)(custom) TAR (of BED, BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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