Chicken chromatin accessibility atlas accelerates epigenetic annotation of birds and gene fine-mapping associated with growth traits
Xiaoning Zhu, 中国农业大学生物学院农业生物技术国家重点实验室, 北京 100193, 中国, Yuzhe Wang, Chong Li, Hanyu Wu, Ran Zhang, Xiaoxiang Hu, 中国农业大学模式动物表型与遗传研究国家重大科技基础设施, 北京 100193, 中国
Abstract
The development of epigenetic maps, such as the ENCODE project in humans, provides resources for gene regulation studies and a reference for research of disease-related regulatory elements. However, epigenetic information, such as a bird-specific chromatin accessibility atlas, is currently lacking for the thousands of bird species currently described. The major genomic difference between birds and mammals is their shorter introns and intergenic distances, which seriously hinders the use of humans and mice as a reference for studying the function of important regulatory regions in birds. In this study, using chicken as a model bird species, we systematically compiled a chicken chromatin accessibility atlas using 53 Assay of Transposase Accessible Chromatin sequencing (ATAC-seq) samples across 11 tissues. An average of 50 796 open chromatin regions were identified per sample, cumulatively accounting for 20.36% of the chicken genome. Tissue specificity was largely reflected by differences in intergenic and intronic peaks, with specific functional regulation achieved by two mechanisms: recruitment of several sequence-specific transcription factors and direct regulation of adjacent functional genes. By integrating data from genome-wide association studies, our results suggest that chicken body weight is driven by different regulatory variants active in growth-relevant tissues. We propose <i>CAB39L</i> (active in the duodenum), <i>RCBTB1</i> (muscle and liver), and novel long non-coding RNA <i>ENSGALG00000053256</i> (bone) as candidate genes regulating chicken body weight. Overall, this study demonstrates the value of epigenetic data in fine-mapping functional variants and provides a compendium of resources for further research on the epigenetics and evolution of birds and mammals.