Downstream targets of HOXB4 in a cell line model of primitive hematopoietic progenitor cells

Dynamic HoxB4-regulatory network during embryonic stem cell differentiation to hematopoietic cells

“…A de novo motif search using the top 500 HoxB4 peaks from each time point successfully identified the HoxB4 DNA-binding motif ( Figure 1D), which matched the HoxB4 binding motif identified by 2 previous studies, 1 using Protein Binding Microarray 18 and the other using ChIP-CHIP. 13 In summary, extensive quality assessment demonstrated that we have generated a high-quality dataset of HoxB4-binding sites across the time course of ESC-to-HSC differentiation.…”

“…Lee et al used a primitive hematopoietic progenitor cell line (EML) and identified 1910 HoxB4 peaks. 13 Oshima et al used an ESC differentiation protocol similar to ours, in which day 6 EB cells were induced by HoxB4 overexpression for 12 days. 12 They identified 2292 HoxB4-binding peaks.…”

“…More recently, using ChIP coupled with a promoter tiling microarray (ChIP-CHIP), 2 studies identified additional HoxB4 target genes in ESC-derived HSCs 12 and in a primitive hematopoietic progenitor cell line, EML. 13 These 2 pioneering studies expanded the set of HoxB4 targets to roughly 3500. Nevertheless, 2 critical questions remain to be answered with regard to the HoxB4 regulatory network.…”

Downregulation of Prdm16 Is Critical for HOXB4-mediated Benign HSC Expansion In Vivo

“…The genes that control this expansion have not been previously identified and are likely relevant for the physiologic regulation of HSC pool size or leukemogenesis in transplanted mice. Prior gene expression profiling studies have identified various HOXB4 target genes in different systems [250][251][252]256,257 yet these studies show little overlap in identified target genes. None of these previous studies included analyses of primary adult HSCs derived directly from HOXB4 transplanted animals.…”

“…Little is known about the mechanism how HOXB4 expands HSCs and at meanwhile prevents leukemogenesis. 251,252 These earlier studies suggested that HOXB4 controls HSC or myeloid progenitors through multiple mechanisms such as apoptosis and symmetric division/proliferation. However, it is noticed that none of the previous studies focused on HOXB4 targets in primary primitive hematopoietic populations in vivo.…”