Large DNA Methylation Nadirs Anchor Chromatin Loops Maintaining Hematopoietic Stem Cell Identity.

Zhang, Xiaotian; Jeong, Mira; Huang, Xingfan; Wang, Xue Qing; Wang, Xinyu; Zhou, Wanding; Shamim, Muhammad S; Gore, Haley; Himadewi, Pamela; Liu, Yushuai; Bochkov, Ivan D; Reyes, Jaime; Doty, Madison; Huang, Yung-Hsin; Jung, Haiyoung; Heikamp, Emily; Aiden, Aviva Presser; Li, Wei; Su, Jianzhong; Aiden, Erez Lieberman; Goodell, Margaret A

Zhang, Xiaotian; Jeong, Mira; Huang, Xingfan; Wang, Xue Qing; Wang, Xinyu; Zhou, Wanding; Shamim, Muhammad S; Gore, Haley; Himadewi, Pamela; Liu, Yushuai; Bochkov, Ivan D; Reyes, Jaime; Doty, Madison; Huang, Yung-Hsin; Jung, Haiyoung; Heikamp, Emily; Aiden, Aviva Presser; Li, Wei; Su, Jianzhong; Aiden, Erez Lieberman; Goodell, Margaret A.

Afiliação

Zhang X; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA; Center for Epigenetics, Van Andel Institute, Grand Rapids, MI, USA. Electronic address: zxtzhangqian@gmail.com.
Jeong M; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
Huang X; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX, USA; Center for Theoretical Biological Physics & Department of Computer Science, Rice University, Houston, TX, USA.
Wang XQ; Center for Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.
Wang X; Institute of Biomedical Big Data, Wenzhou Medical University, Wenzhou, China.
Zhou W; Center for Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.
Shamim MS; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX, USA; Medical Student Training Program, Baylor College of Medicine, Houston, TX, USA; Center for Theoretical Biological Physics & Department of Computer Science, Rice University, Houston, TX, USA.
Gore H; Center for Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.
Himadewi P; Center for Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.
Liu Y; Center for Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.
Bochkov ID; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Reyes J; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Doty M; Molecular Genetic Technology Program, School of Health Professions, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Huang YH; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA; Developmental Biology Program, Baylor College of Medicine, Houston, TX, USA.
Jung H; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA; Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, Korea,
Heikamp E; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Aiden AP; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX, USA; Developmental Biology Program, Baylor College of Medicine, Houston, TX, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Li W; Department of Bioinformatics, Biological Chemistry, University of California, Irvine CA, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
Su J; Institute of Biomedical Big Data, Wenzhou Medical University, Wenzhou, China.
Aiden EL; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX, USA; Center for Theoretical Biological Physics & Department of Computer Science, Rice University, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Shanghai Inst
Goodell MA; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Department of Pediatrics, Baylor Colleg

Mol Cell ; 78(3): 506-521.e6, 2020 05 07.

Article em En | MEDLINE | ID: mdl-32386543

ABSTRACT

ABSTRACT

Higher-order chromatin structure and DNA methylation are implicated in multiple developmental processes, but their relationship to cell state is unknown. Here, we find that large (>7.3 kb) DNA methylation nadirs (termed "grand canyons") can form long loops connecting anchor loci that may be dozens of megabases (Mb) apart, as well as inter-chromosomal links. The interacting loci cover a total of â¼3.5 Mb of the human genome. The strongest interactions are associated with repressive marks made by the Polycomb complex and are diminished upon EZH2 inhibitor treatment. The data are suggestive of the formation of these loops by interactions between repressive elements in the loci, forming a genomic subcompartment, rather than by cohesion/CTCF-mediated extrusion. Interestingly, unlike previously characterized subcompartments, these interactions are present only in particular cell types, such as stem and progenitor cells. Our work reveals that H3K27me3-marked large DNA methylation grand canyons represent a set of very-long-range loops associated with cellular identity.

Assuntos

Cromatina/química; Cromatina/genética; Metilação de DNA; Células-Tronco Hematopoéticas/citologia; Células-Tronco Hematopoéticas/fisiologia; Fator de Ligação a CCCTC/genética; Fator de Ligação a CCCTC/metabolismo; Diferenciação Celular; Cromatina/metabolismo; Proteína Potenciadora do Homólogo 2 de Zeste/genética; Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo; Epigênese Genética; Regulação da Expressão Gênica; Histonas/genética; Histonas/metabolismo; Proteínas de Homeodomínio/genética; Humanos; Hibridização in Situ Fluorescente; Lisina/genética; Lisina/metabolismo; Proteínas Nucleares/genética; Fatores de Transcrição SOXB1/genética; Proteína de Homoeobox de Baixa Estatura/genética; Fatores de Transcrição/genética

Palavras-chave

3D genomics; CpG; DNA methylation; DNA methylation canyon; Polycomb; chromosomal looping; hematopoietic; self-renewal; stem cells

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Hematopoéticas / Cromatina / Metilação de DNA Limite: Humans Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2020 Tipo de documento: Article

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