Integration of multi-omic data to identify transcriptional targets during human hematopoietic stem cell erythroid differentiation

Gene expression is a process through which genetic information is decoded and manufactured into a functional gene product. Different cell types within an organism exhibit distinct biological functions, despite containing the same genetic material, or DNA sequence. This in part can be attributed to the various ways gene expression in a cell is regulated. At a microscopic level, a DNA template is “transcribed” into RNA and then “translated” into a protein, the functional gene product. This process involves the coordination between multiple dynamic events, which are subject to regulation at each step. These regulatory events happen in multiple levels, namely the transcriptional, the posttranscriptional, the translational, and finally, the posttranslational level. Processes integral to multicellular organismal development occur through a series of gene regulatory events, cascading in a gene product that determines cell fate. Proper regulation of gene expression is crucial to the development of healthy living organisms. Since transcription is the very first step of gene expression, predicting transcriptional control that occurs during human development and disease is critical. Combination of multiple genome-wide next-generation sequencing approaches (“multi-omics”) within a particular biological system could be a means to achieve that. This may eventually help in developing therapeutics for human disorders related to the particular tissue type. Here, we have used multiomics by combining ChIP-seq, RNA-seq, and ATAC-seq in human hematopoietic stem and progenitor cells. This approach enabled us highlight certain hitherto unknown transcriptional control mechanisms during red blood cell development from hematopoietic stem cells. The performed analyses were able to predict gene sets, their enhancers, and the hematopoietic master and signaling transcription factors that control them during human red cell differentiation.