Predicting HBZ Interaction with BATF3 Enhancer Regions Through ChIP-seq​

Abstract

Human Lymphotropic Virus Type 1 (HTLV-1) is a complex retrovirus that causes Adult T-cell Leukemia (ATL), an often-fatal form of cancer characterized by uncontrolled proliferation of infected CD4+ T-cells. The viral protein HTLV-1 basic leucine zipper factor (HBZ) has been proven as essential for HTLV-1 proliferation and is believed to contribute to progression to ATL and maintenance of the disease. HBZ functions as a transcriptional regulator. The knock-down of the hbz gene suppresses ATL proliferation, supporting that HBZ is essential for leukemogenesis. Recently, the basic leucine zipper transcription factor ATF-like 3 (BATF3) and interferon regulatory factor 4 (IRF4) were shown to help drive the ATL-specific transcription program. Both BATF3 and IRF4 promote T-cell differentiation and proliferation. HBZ was found to control BATF3 transcription by binding an enhancer region of the BATF3 gene. However, the molecular mechanism used by HBZ to control BATF3 transcription was not resolved. This review utilizes data analyses of chromatin immunoprecipitation specimens evaluated by next generation sequencing (ChIP-seq) to predict how HBZ interacts with the BATF3 enhancer region and then produces the elevated transcription level. ​