The homeobox transcription factor HbxB coordinates distinct gene regulatory networks for asexual development and secondary metabolism in Aspergillus nidulans

Formation of conidia as asexual spores and sometimes worldwide distribution through the air is a very important feature of the fungal life style. This process is controlled by several regulatory proteins, including homeobox domain transcription factors. HbxB is one such regulator with implications in the control of development, secondary metabolism and various stress responses in the filamentous fungus Aspergillus nidulans . However, the molecular mechanism of the regulatory role of HbxB during asexual development is still elusive. Here we show that HbxB is a nuclear localized protein with great impact on asexual sporogenesis. Employment of high throughput assays like chromatin immunoprecipitation (ChIP-seq) and transcriptomics (RNA-seq), elucidated the in vivo binding landscape of HbxB in a genome-wide scale. A set of 238 genes as direct targets of HbxB were identified. A nine bases DNA motif where HbxB prefers to bind in vivo was discovered as HbxB response element (HRE). HbxB is influencing the expression of genes encoding master regulators of the asexual development such as SclB, PpoC, FlbA and FlbC. Moreover, the direct transcriptional control of the secondary metabolites sterigmatocystin and emericellamides biosynthesis by HbxB was discovered. Lastly also a previously elusive mutual regulatory control circuit between HbxB and two major regulators of the asexual development SclB and MsnA was found. Both of these regulators can directly induce the expression of hbxB . This study provides a detailed molecular mechanism on how HbxB controls A. nidulans asexual sporulation.