Project 3: UW-CNOF Biological Validation Development

项目 3:UW-CNOF 生物验证开发

基本信息

  • 批准号:
    9021414
  • 负责人:
  • 金额:
    $ 49.94万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-09-30 至 2020-07-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT – PROJECT 3: UW-CNOF BIOLOGICAL VALIDATION DEVELOPMENT The complexity of hierarchical interactions within the nucleus demands that easy-to-use and accurate methods for mapping and modeling both close-range and long-range interactions be developed. In this project, the experimental and computational methods developed in Projects 1 and 2 will be put to the test to evaluate their ability to detect interactions at high resolution, as well as for the prediction of the sequence determinants of specific aspects of genome architecture. In Aim 1, we will apply newly developed methods to well-defined mouse and human biological systems in which the 4D structure of specific genomic regions and chromosomes can be anticipated. Our validation strategy will employ systems in which alleles can be identified to facilitate studies of diploid cells, i.e. tissues and cell lines from a mouse interspecific cross. Interactions between loci will be tested at enhancer/promoter regions, while interactions at topologically associated domains (TADs) will be tested by comparing the active and inactive X chromosomes in female cells. This functional validation approach will be complemented by high resolution DNA-FISH analyses to verify specific interactions. In Aim 2, to validate our approaches for generating a 4D view of dynamic changes in nuclear structure, we will measure interactions in single cells during the cell cycle and during mouse myoblast and embryonic stem (ES) cell differentiation. By focusing on relatively well understood aspects of these systems, we will achieve validation by linking dynamic changes in the nucleome to other layers of regulation. Analysis of mouse ESC differentiation will exploit the wealth of knowledge that surrounds X inactivation, a process central to nuclear remodeling in mammals, while skeletal myoblast differentiation is well characterized with respect to its transcriptional regulation. In Aim 3, we will validate our ability to predict the sequence determinants of genome architecture. Specifically, we will perform controlled manipulations of defined genomic regions, either by allele- specific heterozygous CRISPR/Cas9 targeting to generate cells with engineered deletions at promoter/enhancer interacting regions and at regions between TADs, or by Xist-mediated silencing of full autosomes. The biological validation work performed in all aims of this project will facilitate the progressive optimization of both bulk and single cell DNase Hi-C protocols (Project 1) and new approaches to modeling the 4D nucleome (Project 2), while also paving the way for biological model development and data generation (Project 4).
项目3:uw-cnof生物验证开发

项目成果

期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
专利数量(0)

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Christine M. Disteche其他文献

Spatial and temporal organization of the genome: Current state and future aims of the 4D nucleome project
基因组的时空组织:4D 核组学项目的现状和未来目标
  • DOI:
    10.1016/j.molcel.2023.06.018
  • 发表时间:
    2023-08-03
  • 期刊:
  • 影响因子:
    16.600
  • 作者:
    Job Dekker;Frank Alber;Sarah Aufmkolk;Brian J. Beliveau;Benoit G. Bruneau;Andrew S. Belmont;Lacramioara Bintu;Alistair Boettiger;Riccardo Calandrelli;Christine M. Disteche;David M. Gilbert;Thomas Gregor;Anders S. Hansen;Bo Huang;Danwei Huangfu;Reza Kalhor;Christina S. Leslie;Wenbo Li;Yun Li;Jian Ma;Sheng Zhong
  • 通讯作者:
    Sheng Zhong
Correction and Clarification: Unusual Molecular Characteristics of a Repeat Sequence Island within a Giemsa-Positive Band on the Mouse X Chromosome
修正和澄清:小鼠 X 染色体吉姆萨阳性条带内重复序列岛的异常分子特征
The Gene for B7, a Costimulatory Signal for T-Cell Activation, Maps to Chromosomal Region 3ql3.3-3q21
  • DOI:
    10.1182/blood.v79.2.489.489
  • 发表时间:
    1992-01-15
  • 期刊:
  • 影响因子:
  • 作者:
    Gordon J. Freeman;Christine M. Disteche;John G. Gribben;David A. Adler;Arnold S. Freedman;James Dougery;Lee M. Nadler
  • 通讯作者:
    Lee M. Nadler
Sceptic: pseudotime analysis for time-series single-cell sequencing and imaging data
  • DOI:
    10.1186/s13059-025-03679-3
  • 发表时间:
    2025-07-17
  • 期刊:
  • 影响因子:
    9.400
  • 作者:
    Gang Li;Hyeon-Jin Kim;Sriram Pendyala;Ran Zhang;Jean-Philippe Vert;Christine M. Disteche;Xinxian Deng;Douglas M. Fowler;William Stafford Noble
  • 通讯作者:
    William Stafford Noble
KDM6A facilitates Xist upregulation at the onset of X inactivation
KDM6A 促进 X 失活开始时 Xist 的上调
  • DOI:
    10.1186/s13293-024-00683-3
  • 发表时间:
    2025-01-03
  • 期刊:
  • 影响因子:
    5.100
  • 作者:
    Josephine Lin;Jinli Zhang;Li Ma;He Fang;Rui Ma;Camille Groneck;Galina N. Filippova;Xinxian Deng;Chizuru Kinoshita;Jessica E. Young;Wenxiu Ma;Christine M. Disteche;Joel B. Berletch
  • 通讯作者:
    Joel B. Berletch

Christine M. Disteche的其他文献

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{{ truncateString('Christine M. Disteche', 18)}}的其他基金

Dissecting the role of sex-linked genes and APOE e4 risk in AD
剖析 AD 中性相关基因和 APOE e4 风险的作用
  • 批准号:
    10299469
  • 财政年份:
    2021
  • 资助金额:
    $ 49.94万
  • 项目类别:
Dissecting the role of sex-linked genes and APOE e4 risk in AD
剖析 AD 中性相关基因和 APOE e4 风险的作用
  • 批准号:
    10677855
  • 财政年份:
    2021
  • 资助金额:
    $ 49.94万
  • 项目类别:
UW 4-Dimensional Genomic Organization of Mammalian Embryogenesis Center
威斯康星大学哺乳动物胚胎发生中心 4 维基因组组织
  • 批准号:
    10441525
  • 财政年份:
    2020
  • 资助金额:
    $ 49.94万
  • 项目类别:
UW 4-Dimensional Genomic Organization of Mammalian Embryogenesis Center
威斯康星大学哺乳动物胚胎发生中心 4 维基因组组织
  • 批准号:
    10885341
  • 财政年份:
    2020
  • 资助金额:
    $ 49.94万
  • 项目类别:
UW 4-Dimensional Genomic Organization of Mammalian Embryogenesis Center
威斯康星大学哺乳动物胚胎发生中心 4 维基因组组织
  • 批准号:
    10669573
  • 财政年份:
    2020
  • 资助金额:
    $ 49.94万
  • 项目类别:
UW 4-Dimensional Genomic Organization of Mammalian Embryogenesis Center
威斯康星大学哺乳动物胚胎发生中心 4 维基因组组织
  • 批准号:
    10265565
  • 财政年份:
    2020
  • 资助金额:
    $ 49.94万
  • 项目类别:
X chromosome regulation and role in aneuploidy
X 染色体调控及其在非整倍性中的作用
  • 批准号:
    10614939
  • 财政年份:
    2019
  • 资助金额:
    $ 49.94万
  • 项目类别:
X chromosome regulation and role in aneuploidy
X 染色体调控及其在非整倍性中的作用
  • 批准号:
    9908109
  • 财政年份:
    2019
  • 资助金额:
    $ 49.94万
  • 项目类别:
X chromosome regulation and role in aneuploidy
X 染色体调控及其在非整倍性中的作用
  • 批准号:
    10395506
  • 财政年份:
    2019
  • 资助金额:
    $ 49.94万
  • 项目类别:
DOSAGE COMPENSATION OF THE ACTIVE X CHROMOSOME IN MAMMALS
哺乳动物中活性 X 染色体的剂量补偿
  • 批准号:
    7183757
  • 财政年份:
    2007
  • 资助金额:
    $ 49.94万
  • 项目类别:

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