PLX322851

GSE99009: SUMO safeguards somatic and pluripotent cell identities by enforcing distinct chromatin states

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Purposes: (1) compare the SUMO chromatin landscape between mouse embryonic fibroblasts (MEFs) and embryonic stem cells (ESc) (2) Decipher how hyposumoylation enhances MEF to induced pluripotent stem cells (iPSc) reprogramming (3) Decipher how hyposumoylation enhances ESc to 2C-like cells conversion. Methods : (1) ChIP-seq in MEFs and ESc for SUMO isoforms and histone marks. (2) ChIP-seq for transcription factors and histone marks at day 4 of MEF to iPSc reprogramming comparing wild type (shCtrl) and hyposumoylated cells (shUbc9). ATAC-Seq at day 4 of MEF to iPSc reprogramming comparing wild type (shCtrl) and hyposumoylated cells (shUbc9). RNA-Seq in MEFs, iPSc, at day 4 and day 7 of MEF to iPSc reprogramming comparing wild type (shCtrl) and hyposumoylated cells (shUbc9). (3) RNA-Seq in ESc comparing wild-type (siCtrl) and hyposumoylated cells (siUbc9). Results: (1) SUMO chromatin landscape is highly different between MEFs and ESc and associates to distinct chromatin marks. (2) Hyposumoylation enhances MEFs to iPSc reprogramming by favoring the extinction of the MEF transcriptional program and redistributing pluripotency factors from MEF enhancers toward ES enhancers. (3) Hyposumoylation enhances ES to 2C-like conversion by destabilizing heterochromatin thus resulting in an activation of the 2-cell transcriptional program. Conclusion: SUMO at chromatin is gate-keeper of cell-identity. SOURCE: Claudia ChicaBiostatistics and Bioinformatics Hub Institut Pasteur