In this episode of the Epigenetics Podcast, we talked with Dr. Joseph Ecker from the Salk Institute about his work on high-resolution genome-wide mapping technologies, specifically how the regulation of gene expression is influenced by DNA methylation, chromatin accessibility, and non-coding RNAs across various cell types and developmental stages.

During our conversation, we delve into Dr. Ecker's contributions to the characterization of the genome of Arabidopsis thaliana, a project pivotal in the plant genomics field, where he collaborated on the early sequencing efforts that dramatically outpaced expectations. He highlights the technological advancements that enabled such efficient sequencing and how this foundational work opened new avenues for exploring transcriptional activity.

We also discuss Dr. Ecker’s pivotal work on the comprehensive DNA methylation map of Arabidopsis, which he developed in collaboration with other researchers. This groundbreaking study established the links between methylation patterns and gene expression, paving the way for further research into how these epigenetic marks influence over gene regulation. He elaborates on the significance of transitioning from traditional methods to more sophisticated techniques, such as RNA-seq, and the lessons learned from sequencing projects that have since been applied to human biology.

Dr. Ecker's transition to studying human cells is further explored as he discusses the profiling of DNA methylation in induced pluripotent stem cells (iPSCs), revealing how epigenetic memory can influence cellular differentiation and development. He underscores the importance of understanding these methylation patterns, particularly as they relate to conditions like Alzheimer's disease and stem cell biology, where he examines potential applications of his findings in medical research.

As our conversation progresses, we touch upon Dr. Ecker's ongoing projects that utilize advanced multi-omic techniques to investigate the epigenomes of the human brain, focusing on how DNA methylation and gene expression change with age and in the context of neurodegenerative diseases. He details the collaboration efforts with various consortia aimed at cataloging gene regulatory networks and understanding the complex interactions that take place within the brain throughout different life stages.

Mozo T, Dewar K, Dunn P, Ecker JR, Fischer S, Kloska S, Lehrach H, Marra M, Martienssen R, Meier-Ewert S, Altmann T. A complete BAC-based physical map of the Arabidopsis thaliana genome. Nat Genet. 1999 Jul;22(3):271-5. doi: 10.1038/10334. PMID: 10391215.

Zhang X, Yazaki J, Sundaresan A, Cokus S, Chan SW, Chen H, Henderson IR, Shinn P, Pellegrini M, Jacobsen SE, Ecker JR. Genome-wide high-resolution mapping and functional analysis of DNA methylation in arabidopsis. Cell. 2006 Sep 22;126(6):1189-201. doi: 10.1016/j.cell.2006.08.003. Epub 2006 Aug 31. PMID: 16949657.

Lister R, O'Malley RC, Tonti-Filippini J, Gregory BD, Berry CC, Millar AH, Ecker JR. Highly integrated single-base resolution maps of the epigenome in Arabidopsis. Cell. 2008 May 2;133(3):523-36. doi: 10.1016/j.cell.2008.03.029. PMID: 18423832; PMCID: PMC2723732.

Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009 Nov 19;462(7271):315-22. doi: 10.1038/nature08514. Epub 2009 Oct 14. PMID: 19829295; PMCID: PMC2857523.

Lister R, Pelizzola M, Kida YS, Hawkins RD, Nery JR, Hon G, Antosiewicz-Bourget J, O'Malley R, Castanon R, Klugman S, Downes M, Yu R, Stewart R, Ren B, Thomson JA, Evans RM, Ecker JR. Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature. 2011 Mar 3;471(7336):68-73. doi: 10.1038/nature09798. Epub 2011 Feb 2. Erratum in: Nature. 2014 Oct 2;514(7520):126. PMID: 21289626; PMCID: PMC3100360.

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