Program: Oral and Poster Abstracts
Session: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster III
Genome wide analysis of CBP and p300 enrichment showed these co-factors are highly enriched in introns and intergenic regions than the gene promoters suggesting that these co-activators efficiently mark enhancers in the haematopoietic stem cells and erythroid cells. Co-localization of CBP/p300 with erythroid transcription factors (GATA1, KLF1, NFE2 and TAL1) was performed. The results showed that CBP/p300 are highly associated with erythroid transcription factors during differentiation indicating that transcriptional activator complexes consisting of these transcription factors and CBP/p300 in enhancer mediated transcriptional regulation in erythropoiesis. The sites of CBP/p300 occupancy were correlated with the transcriptome data and it was found that most of the top regulated genes were enriched with CBP and p300 within the intronic region in erythroid cells. We then explored whether CBP and p300 are enriched in the regions associated with DNA polymorphisms relevant to erythroid cell traits and observed that CBP/p300occupy at HBD (5’UTR), BCL11A (intron 2) and HBS1L-MYB intergenic region which contains polymorphisms linked with levels of fetal haemoglobin (HbF). We also found enrichment of these co-activators in previously mapped erythroid specific enhancers such as IKZF1, ANK1 and ABOgene loci.
Gene ontology (GO) was performed using GREAT for regions associated with CBP and p300 (binomial fold enrichment >4) and the results indicated that the genes associated with CBP were involved in erythrocyte development whereas the genes associated with p300 were found to regulate erythroid differentiation. These erythroid specific genes delineated in our study also showed conservation in mouse and were found to be associated with erythroid cell phenotypes. We also found significant enrichment of CBP and p300 in erythroid cells compared to haematopoietic stem cells for several genes that have not been previously characterized for erythroid differentiation. Taken together, our findings elucidated the roles of co-activators CBP and p300 in erythroid differentiation and further we identified these factors are enriched in previously known and new erythroid specific enhancers in association with cell specific transcription factors. Functional evaluation of the newly idenfied regulatory elements bound by CBP and p300 in the erythroid cells will provide insights in to erythroid cell development and differentiation.
Disclosures: No relevant conflicts of interest to declare.
See more of: Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron
See more of: Oral and Poster Abstracts
*signifies non-member of ASH