Genetic determinants and epigenetic effects of pioneer-factor occupancy.
Julie DonagheySudhir ThakurelaJocelyn CharltonJennifer S ChenZachary D SmithHongcang GuRamona PopKendell ClementElena K StamenovaRahul KarnikDavid R KelleyCasey A GiffordDavide CacchiarelliJohn L RinnAndreas GnirkeMichael J ZillerAlexander MeissnerPublished in: Nature genetics (2018)
Transcription factors (TFs) direct developmental transitions by binding to target DNA sequences, influencing gene expression and establishing complex gene-regultory networks. To systematically determine the molecular components that enable or constrain TF activity, we investigated the genomic occupancy of FOXA2, GATA4 and OCT4 in several cell types. Despite their classification as pioneer factors, all three TFs exhibit cell-type-specific binding, even when supraphysiologically and ectopically expressed. However, FOXA2 and GATA4 can be distinguished by low enrichment at loci that are highly occupied by these factors in alternative cell types. We find that expression of additional cofactors increases enrichment at a subset of these sites. Finally, FOXA2 occupancy and changes to DNA accessibility can occur in G1-arrested cells, but subsequent loss of DNA methylation requires DNA replication.
Keyphrases
- dna methylation
- genome wide
- gene expression
- transcription factor
- copy number
- single cell
- circulating tumor
- single molecule
- cell therapy
- induced apoptosis
- cell free
- poor prognosis
- dna binding
- deep learning
- optical coherence tomography
- genome wide identification
- signaling pathway
- diabetic retinopathy
- long non coding rna
- high resolution
- bone marrow
- cell cycle arrest
- circulating tumor cells
- atomic force microscopy