Identification of several potential chromatin binding sites of HOXB7 and its downstream target genes in breast cancer

Abstract

HOXB7 encodes a transcription factor that is overexpressed in a number of cancers and encompasses many oncogenic functions. Previous results have shown it to promote cell proliferation, angiogenesis, epithelial-mesenchymal transition, DNA repair and cell survival. Because of its role in many cancers and tumorigenic processes, HOXB7 has been suggested to be a potential drug target. However, HOXB7 binding sites on chromatin and its targets are poorly known. The aim of our study was to identify HOXB7 binding sites on breast cancer cell chromatin and to delineate direct target genes located nearby these binding sites. We found 1,504 HOXB7 chromatin binding sites in BT-474 breast cancer cell line that overexpresses HOXB7. Seventeen selected binding sites were validated by ChIP-qPCR in several breast cancer cell lines. Furthermore, we analyzed expression of a large number of genes located nearby HOXB7 binding sites and found several new direct targets, such as CTNND2 and SCGB1D2. Identification of HOXB7 chromatin binding sites and target genes is essential to understand better the role of HOXB7 in breast cancer and mechanisms by which it regulates tumorigenic processes. What's new? The transcription factor HOXB7 is overexpressed in various cancers, but it's not yet known just which genes HOXB7 activates. How does it influence cancer on a molecular level? This study found 1500 sequences where HOXB7 binds the chromatin in breast cancer cells. They went on to identify several potential target genes near the HOXB7 binding sites. Not only will finding these genes help explain how HOXB7 overexpression promotes tumor growth, it will help understand what side effects might result from hindering HOXB7 expression.