title: CTCF and CohesinSA-1 Mark Active Promoters and Boundaries of Repressive Chromatin Domains in Primary Human Erythroid Cells.
abstract: CTCF and cohesinSA-1 are regulatory proteins involved in a number of critical cellular processes including transcription, maintenance of chromatin domain architecture, and insulator function. To assess changes in the CTCF and cohesinSA-1 interactomes during erythropoiesis, chromatin immunoprecipitation coupled with high throughput sequencing and mRNA transcriptome analyses via RNA-seq were performed in primary human hematopoietic stem and progenitor cells (HSPC) and primary human erythroid cells from single donors.
  
  
  
  Sites of CTCF and cohesinSA-1 co-occupancy were enriched in gene promoters in HSPC and erythroid cells compared to single CTCF or cohesin sites. Cell type-specific CTCF sites in erythroid cells were linked to highly expressed genes, with the opposite pattern observed in HSPCs. Chromatin domains were identified by ChIP-seq with antibodies against trimethylated lysine 27 histone H3, a modification associated with repressive chromatin. Repressive chromatin domains increased in both number and size during hematopoiesis, with many more repressive domains in erythroid cells than HSPCs. CTCF and cohesinSA-1 marked the boundaries of these repressive chromatin domains in a cell-type specific manner.
  
  
  
  These genome wide data, changes in sites of protein occupancy, chromatin architecture, and related gene expression, support the hypothesis that CTCF and cohesinSA-1 have multiple roles in the regulation of gene expression during erythropoiesis including transcriptional regulation at gene promoters and maintenance of chromatin architecture. These data from primary human erythroid cells provide a resource for studies of normal and perturbed erythropoiesis.
authors.affiliation: Department of Pediatrics, University of Rochester, Rochester, New York, United States of America.
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Steiner
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Vincent
authors.initials: V
authors.lastname: Schulz
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Yelena
authors.initials: Y
authors.lastname: Makismova
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Lezon-Geyda
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, United States of America.|Departments of Pathology and Genetics, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Gallagher
mesh_terms: D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism; D004920:Erythropoiesis; D020869:Gene Expression Profiling / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D020014:K562 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D060066:Protein Interaction Maps; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA / Q000379:methods
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; D009687:Nuclear Proteins; D012097:Repressor Proteins; C108522:STAG1 protein, human