SNF5 is an essential executor of epigenetic regulation in pluripotency and differentiation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: jueng soo You
PROVIDER: E-GEOD-36140 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:We report the application of single-molecule-based sequencing technology for high-throughput profiling of SNF5 binding in human pluripotent embryonic carcinoma NCCIT and SNF5 overexpressed NCCIT cells. We generated genome-wide cSNF5 maps of NCCIT and SNF5 overexpressed NCCIT cells from chromatin immunoprecipitated DNA. SNF5 and OCT4 seem not to share their binding in OCT4 centered binding plot in control, while SNF5 overexpression directs SNF5 to OCT4 target genes. Examination of the relationship between SNF5 and OCT4 binding in control and SNF5 overexpressed cells.
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Project description:The t(8;21) translocation fuses the DNA binding domain of the hematopoietic master regulator RUNX1 to the ETO protein. The resultant RUNX1/ETO fusion protein is a leukemia-initiating transcription factor that interferes with RUNX1 function. The result of this interference is a block in differentiation and, finally, the development of acute myeloid leukemia (AML). To obtain insights into RUNX1/ETO-dependant alterations of the epigenetic landscape we measured genome-wide RUNX1- and RUNX1/ETO bound regions in t(8;21) cells and assessed to what extent the effects of RUNX1/ETO on the epigenome depend on its continued expression in established leukemic cells. To this end we determined dynamic alterations of histone acetylation, RNA Polymerase II binding and RUNX1 occupancy in the presence or absence of RUNX1/ETO using a knockdown approach. Combined global assessments of chromatin accessibility and kinetic gene expression data show that RUNX1/ETO controls the expression of important regulators of hematopoietic differentiation and self-renewal. We show that selective removal of RUNX1/ETO leads to a widespread reversal of epigenetic reprogramming and a genome-wide re-distribution of RUNX1 binding, resulting in the inhibition of leukemic proliferation and self-renewal and the induction of differentiation. This demonstrates that RUNX1/ETO represents a pivotal therapeutic target in AML. RUNX1 siMM and RUNX1 siRE ChIP-Seq samples and a paired-end ChIP-Seq samples from patients with t(8;21) AML are used in this study; there are two paired-end ChIP-Seq runs and control per patient
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