Functional annotation of the cattle genome through systematic discovery and characterization of chromatin states and butyrate-induced variations

Lingzhao Fang, Shuli Liu, Mei Liu, Xiaolong Kang, Shudai Lin, Bingjie Li, Erin E. Connor, Ransom L. Baldwin VI, Albert Tenesa, Li Ma, George E Liu, Cong-Jun Li

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Background: The functional annotation of genomes, including chromatin accessibility and modifications, is important for understanding and effectively utilizing the increased amount of genome sequences reported. However, while such annotation has been well explored in a diverse set of tissues and cell types in human and model organisms, relatively little data are available for livestock genomes, hindering our understanding of complex trait variation, domestication, and adaptive evolution. Here, we present the first complete global landscape of
regulatory elements in cattle and explore the dynamics of chromatin states in rumen epithelial cells induced by the rumen developmental regulator—butyrate.

Results: We established the first global map of regulatory elements (15 chromatin states) and defined their coordinated activities in cattle, through genome-wide profiling for six histone modifications, RNA polymerase II,
CTCF-binding sites, DNA accessibility, DNA methylation, and transcriptome in rumen epithelial primary cells (REPC), rumen tissues, and Madin-Darby bovine kidney epithelial cells (MDBK). We demonstrated that each chromatin state
exhibited specific enrichment for sequence ontology, transcription, methylation, trait-associated variants, gene expression-associated variants, selection signatures, and evolutionarily conserved elements, implying distinct
biological functions. After butyrate treatments, we observed that the weak enhancers and flanking active transcriptional start sites (TSS) were the most dynamic chromatin states, occurred concomitantly with significant
alterations in gene expression and DNA methylation, which was significantly associated with heifer conception rate
and stature economic traits.

Conclusion: Our results demonstrate the crucial role of functional genome annotation for understanding genome regulation, complex trait variation, and adaptive evolution in livestock. Using butyrate to induce the dynamics of
the epigenomic landscape, we were able to establish the correlation among nutritional elements, chromatin states, gene activities, and phenotypic outcomes.
Original languageEnglish
JournalBMC Biology
Publication statusPublished - 16 Aug 2019

Keywords / Materials (for Non-textual outputs)

  • Cattle genome
  • Functional annotation
  • Chromatin states
  • Butyrate,
  • Rumen development


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