Epigenetic memory at embryonic enhancers identified in DNA methylation maps from adult mouse tissues
TLDR
By mapping base-resolution methylomes in adult mouse tissues at shallow coverage, this work identifies 302,864 tissue-specific differentially methylated regions (tsDMRs) and estimates that >6.7% of the mouse genome is variably methylated, and suggests that epigenetic memory of embryonic development may be retained in adult tissues.Abstract:
Mammalian development requires cytosine methylation, a heritable epigenetic mark of cellular memory believed to maintain a cell's unique gene expression pattern. However, it remains unclear how dynamic DNA methylation relates to cell type-specific gene expression and animal development. Here, by mapping base-resolution methylomes in 17 adult mouse tissues at shallow coverage, we identify 302,864 tissue-specific differentially methylated regions (tsDMRs) and estimate that >6.7% of the mouse genome is variably methylated. Supporting a prominent role for DNA methylation in gene regulation, most tsDMRs occur at distal cis-regulatory elements. Unexpectedly, some tsDMRs mark enhancers that are dormant in adult tissues but active in embryonic development. These 'vestigial' enhancers are hypomethylated and lack active histone modifications in adult tissues but nevertheless exhibit activity during embryonic development. Our results provide new insights into the role of DNA methylation at tissue-specific enhancers and suggest that epigenetic memory of embryonic development may be retained in adult tissues.read more
Citations
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A pig BodyMap transcriptome reveals diverse tissue physiologies and evolutionary dynamics of transcription.
Long Jin,Qianzi Tang,Silu Hu,Zhongxu Chen,Xuming Zhou,Bo Zeng,Yuhao Wang,Mengnan He,Yan Li,Lixuan Gui,Linyuan Shen,Keren Long,Jideng Ma,Xun Wang,Zhengli Chen,Yanzhi Jiang,Guoqing Tang,Li Zhu,Fei Liu,Bo Zhang,Zhiqing Huang,Guisen Li,Diyan Li,Vadim N. Gladyshev,Jingdong Yin,Yiren Gu,Xuewei Li,Mingzhou Li +27 more
TL;DR: A comprehensive transcriptomic survey of pigs can provide a mechanistic understanding of tissue specialization processes underlying economically valuable traits and accelerate their use as a biomedical model as discussed by the authors, which can facilitate adoption of pigs as a model for human biology and disease and uncover the molecular bases of valuable traits.
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Reprogramming of the FOXA1 cistrome in treatment-emergent neuroendocrine prostate cancer
Sylvan C. Baca,Sylvan C. Baca,David Y. Takeda,Ji-Heui Seo,Justin H. Hwang,Sheng-Yu Ku,Rand Arafeh,Taylor E. Arnoff,Supreet Agarwal,Connor Bell,Edward P. O’Connor,Xintao Qiu,Sarah Abou Alaiwi,Rosario I. Corona,Marcos A. S. Fonseca,Claudia Giambartolomei,Claudia Giambartolomei,Paloma Cejas,Klothilda Lim,Monica He,Anjali V. Sheahan,Amin Nassar,Jacob E. Berchuck,Lisha G. Brown,Holly M. Nguyen,Ilsa Coleman,Arja Kaipainen,Navonil De Sarkar,Peter S. Nelson,Colm Morrissey,Keegan Korthauer,Mark Pomerantz,Leigh Ellis,Leigh Ellis,Bogdan Pasaniuc,Kate Lawrenson,Kathleen Kelly,Amina Zoubeidi,Amina Zoubeidi,William C. Hahn,William C. Hahn,Himisha Beltran,Henry W. Long,Myles Brown,Eva Corey,Matthew L. Freedman,Matthew L. Freedman +46 more
TL;DR: The data establish the importance of FOXA1 in NEPC and provide a principled approach to identifying novel cancer dependencies through epigenomic profiling.
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Distinct contributions of DNA methylation and histone acetylation to the genomic occupancy of transcription factors
Martin Cusack,Hamish W King,Paolo Spingardi,Benedikt M. Kessler,Robert J. Klose,Skirmantas Kriaucionis +5 more
TL;DR: The pronounced additive effect of HDAC inhibition in DNA methylation-deficient cells demonstrates thatDNA methylation and histone deacetylation act largely independently to suppress transcription factor binding and gene expression.
Journal ArticleDOI
Retinoid-Sensitive Epigenetic Regulation of the Hoxb Cluster Maintains Normal Hematopoiesis and Inhibits Leukemogenesis
Pengxu Qian,Bony De Kumar,Xi C. He,Christof Nolte,Madelaine Gogol,Youngwook Ahn,Shiyuan Chen,Zhenrui Li,Zhenrui Li,Hanzhang Xu,John M. Perry,Deqing Hu,Deqing Hu,Fang Tao,Fang Tao,Meng Zhao,Yingli Han,Kate Hall,Allison Peak,Ariel Paulson,Chongbei Zhao,Aparna Venkatraman,Andrew C. Box,Anoja Perera,Jeffrey S. Haug,Tari Parmely,Hua Li,Robb Krumlauf,Robb Krumlauf,Linheng Li,Linheng Li +30 more
TL;DR: Findings demonstrate pivotal roles for retinoid signaling and the DERARE in maintaining HSCs and preventing leukemogenesis by coordinate regulation of Hoxb genes.
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Epigenetic foundations of pluripotent stem cells that recapitulate in vivo pluripotency
TL;DR: The developmental potential and epigenetic regulation of pluripotent stem cells in rodents and humans in vitro is described and unsolved issues in developing strategies to capture in vivo pluripotency in vitro are discussed.
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