The genome-wide impact of nipblb loss-of-function on zebrafish gene expression

Transcriptional changes normally occur during development but also underlie differences between healthy and pathological conditions. Transcription factors or chromatin modifiers are involved in orchestrating gene activity, such as the cohesin genes and their regulator NIPBL. In our previous studies, using a zebrafish model for nipblb knock-down, we described the effect of nipblb loss-of-function in specific contexts such as central nervous system development and hematopoiesis. However, the genome-wide transcriptional impact of nipblb loss-of-function in zebrafish embryos at diverse developmental stages remains under investigated. By RNA-seq analyses in zebrafish embryos at 24 hours post fertilization, we examined genome-wide effects of nipblb haploinsufficiency on transcriptional programs. Differential gene expression analysis revealed that nipblb loss-of-function has a major impact on gene expression at 24 hours post fertilization, and that this massive transcriptional dysregulation is rescued by specific back-up mechanisms that counteract the transcriptional patterns induced by nipblb silencing. Moreover, we unraveled a connection between nipblb-dependent differential expression and gene expression patterns of hematological cell populations and AML subtypes, enforcing our previous evidences on the involvement of NIPBL-related transcriptional dysregulation in hematological malignancies.