Canonical and non-canonical JAK/STAT transcriptional targets may be involved in distinct and overlapping cellular processes

BMC Genomics

Research Article

Willis X. Li¹  Amy Tsurumi²  Connie Zhao³ 

[1] Department of Medicine, University of California at San Diego, 9500 Gilman Dr, 92093, La Jolla, CA, USA;Department of Surgery, Massachusetts General Hospital, 50 Blossom St., Thier 340, 02114, Boston, MA, USA;Department of Microbiology and Immunology, Harvard Medical School, 77 Ave. Louis Pasteur, 02115, Boston, MA, USA;Shriners Hospitals for Children-Boston®, 51 Blossom St, 02114, Boston, MA, USA;Genomics Resource Center, The Rockefeller University, New York, NY, USA;

关键词: JAK;    STAT;    Non-canonical JAK/STAT signaling;    Drosophila;    Development;    Signal transduction;    Epigenetics;    Heterochromatin;   

DOI  :  10.1186/s12864-017-4058-y

 received in 2016-11-11, accepted in 2017-08-14,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway has been well-characterized as a crucial signal transduction cascade that regulates vital biological responses including development, immunity and oncogenesis. Additionally to its canonical pathway that uses the phosphorylated form of the STAT transcription factor, recently the non-canonical pathway involving heterochromatin formation by unphosphorylated STAT was recently uncovered. Considering the significant role of the JAK/STAT pathway, we used the simple Drosophila system in which the non-canonical pathway was initially characterized, to compare putative canonical versus non-canonical transcriptional targets across the genome. We analyzed microarray expression patterns of wildtype, Jak gain- and loss-of-function mutants, as well as the Stat loss-of-function mutant during embryogenesis, since the contribution of the canonical signal transduction pathway has been well-characterized in these contexts. Previous studies have also demonstrated that Jak gain-of-function and Stat mutants counter heterochromatin silencing to de-repress target genes by the non-canonical pathway.ResultsCompared to canonical target genomic loci, non-canonical targets were significantly more associated with sites enriched with heterochromatin-related factors (p = 0.004). Furthermore, putative canonical and non-canonical transcriptional targets identified displayed some differences in biological pathways they regulate, as determined by Gene Ontology (GO) enrichment analyses. Canonical targets were enriched mainly with genes relevant to development and immunity, as expected, whereas the non-canonical target gene set mainly showed enrichment of genes for various metabolic responses and stress response, highlighting the possibility that some differences may exist between the two loci.ConclusionsCanonical and non-canonical JAK/STAT genes may regulate distinct and overlapping sets of genes and may perform specific overall functions in physiology. Further studies at different developmental stages, or using distinct tissues may identify additional targets and provide insight into which gene targets are unique to the canonical or non-canonical pathway.

【 授权许可】

CC BY   
© The Author(s). 2017