Acoel genome reveals the regulatory landscape of whole-body regeneration

• Published in: Science (American Association for the Advancement of Science) Vol. 363; no. 6432
• Main Authors: Gehrke, Andrew R, Neverett, Emily, Luo, Yi-Jyun, Brandt, Alexander, Ricci, Lorenzo, Hulett, Ryan E, Gompers, Annika, Ruby, J Graham, Rokhsar, Daniel S, Reddien, Peter W, Srivastava, Mansi
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 15-03-2019
• Subjects: Accessibility; Amputation; Animals; Binding Sites; Chromatin; Chromatin - metabolism; Coding; Dynamic response; Early Growth Response Transcription Factors - metabolism; Gene expression; Gene Expression Regulation; Gene Regulatory Networks; Gene sequencing; Genes; Genome; Genomes; Genomics; Hofstenia; Hofstenia miamia; Homology; Interference; Invertebrates - genetics; Invertebrates - physiology; Literary Devices; Muscles; Networks; Nucleotide sequence; Proteins; Regeneration; Regeneration - genetics; Regulatory sequences; Ribonucleic acid; RNA; RNA-mediated interference; Skin; Stem cells; Target recognition; Transcription factors; Transcriptome; Transposase; Wound Healing - genetics; Wounding
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aau6173

Whole-body regeneration is accompanied by complex transcriptomic changes, yet the chromatin regulatory landscapes that mediate this dynamic response remain unexplored. To decipher the regulatory logic that orchestrates regeneration, we sequenced the genome of the acoel worm
, a highly regenerative member of the sister lineage of other bilaterians. Epigenomic profiling revealed thousands of regeneration-responsive chromatin regions and identified dynamically bound transcription factor motifs, with the early growth response (EGR) binding site as the most variably accessible during
regeneration. Combining
inhibition with chromatin profiling suggests that Egr functions as a pioneer factor to directly regulate early wound-induced genes. The genetic connections inferred by this approach allowed the construction of a gene regulatory network for whole-body regeneration, enabling genomics-based comparisons of regeneration across species.