Genome wide chromatin modification associated with the developmental transition from brown to white adipose tissue

Chromatin immunoprecipitation coupled with Next Generation Sequencing (NGS) was used to find regions enriched for the histone modifications, H3K27me3, H3K27ac and H3K4me3 in perirenal adipose tissue in late gestation sheep fetuses, (i.e.~ 2 weeks before birth) and 12 week old lambs. This was undertaken to investigate the epigenetic changes that occur as a result of development during this key period where the perirenal adipose tissue transitions from a primarily brown adipose tissue state to a primarily white adipose tissue state. The former tissue has a primary role in maintaining thermogenesis in new-born mammals while the latter acts as an energy storage vehicle that enhances survival when food is limiting. Both tissues are involved in maintaining energy homeostasis in adults and are strongly implicated in chronic metabolic diseases associated with obesity in humans. Little is known about this developmental process in terms of mechanism and changes in gene expression. This developmental contrast revealed that this developmental transition is associated with large changes in chromatin modifications associated with the morphological change of the tissue during this brief period. Overall design: Genome wide chromatin modification profiles for H3K27me3, H3K27ac and H3K4me3 of perirenal adipose tissue from sheep fetuses at 132 days of gestation (132 d post conception (dpc); term =150±3d) and lambs 80 days after birth were generated by deep sequencing using Illumina GA11X or HiSeq2000 sequencing platform. Two biological replicates for each developmental timepoint were analyzed except for H3K4me3, where n=3/gp was used for the lamb sample and n=2/gp for the fetal sample. The sequence reads that passed quality filters were mapped to sheep genome assembly OARv3.1.74 using the mapping protocol in the CLC Genomics Workbench (v7.0).