The evolution of genomic imprinting

基因组印记的进化

基本信息

批准号：
10321267
负责人：
Jeffrey Good
金额：
$ 28.92万
依托单位：
UNIVERSITY OF MONTANA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10321267
关键词：
Alleles Atlases Biodiversity Biological Models Candidate Disease Gene Chromatin Structure Complex Congenital Disorders DNA Methylation Data Development Developmental Process Disease model Dwarfism Dysplasia Embryonic Development Epigenetic Process Evolution Failure Fetal Development Gene Expression Gene Expression Regulation Genes Genetic Genetic Transcription Genetic study Genome Genomic Imprinting Genomic approach Genotype Goals Growth Growth Disorders Hamsters House mice Human Hybrids Knowledge Link Mammals Modeling Molecular Genetics Mus Parents Pathology Pathway interactions Phenotype Placenta Placentation Play Recurrence Regulation Regulator Genes Regulatory Pathway Research Research Project Grants Rodent Rodent Model Role Series Syndrome System Testing Variant X Chromosome comparative comparative genomics developmental disease epigenetic silencing epigenomics experimental study fascinate follow-up gene regulatory network genetic approach genetic architecture genome-wide genomic data imprint insight interest mammalian genome novel programs reproductive trait transcriptomics

项目摘要

Genomic imprinting is a form of epigenetic gene regulation that plays a key role in placental development. Imprinted expression is highly enriched within developmental pathways and, as a consequence, the disruption of imprinted pathways results in a range of congenital developmental disorders in humans and other mammals. Mammalian hybrids often manifest many of the same placental growth abnormalities, raising the intriguing possibility that recurrent developmental syndromes within and between species may reflect the disruption of common regulatory pathways. However, surprisingly little is known about the evolution of imprinted regulatory networks, and the contribution of disrupted genomic imprinting to the evolution of reproductive barriers between species remains unresolved. The proposed research will begin to overcome these fundamental gaps in knowledge by generating novel comparative genomic data on placental gene expression and genomic imprinting among closely related species and their reciprocal hybrids. Specific Aims 1 and 2 will use a series of hybrid rodent systems to generate an atlas of genome-wide placental transcription, DNA methylation, and chromatin structure across five species and two major lineages of rodents (house mice and dwarf hamsters). These unprecedented comparative data will allow us to resolve the basic epigenetic mechanisms controlling genomic imprinting and quantify how placental expression and imprinting has evolved over 30 million years of divergence. Specific Aim 3 will use a systems genetics approach to examine the genetic architecture of hybrid overgrowth, placental expression, and imprinting in dwarf hamsters and mice. These experiments will allow us to understand the mechanistic and genetic underpinnings of a common form of placental dysplasia and test the novel hypothesis the X chromosome plays a central role in the regulation of imprinted autosomal regulatory networks. The long-term goals of this research program are to (1) illuminate the basic epigenetic mechanisms controlling genomic imprinting, (2) provide insights into the evolutionary tempo and theoretical drivers of imprinting and other aspects of placental expression, (3) test hypotheses on the causal connection between disrupted imprinting and abnormal placental development, (4) understand the organization and evolution of imprinted expression networks, and (5) link these conceptual advances to understand the contribution of genomic imprinting to the origin of biological diversity.

基因组印记是一种表观遗传基因调控的一种形式，在胎盘中起关键作用发展。印迹表达在发育途径中高度丰富，作为一个结果，印迹途径的破坏导致一系列先天性人类和其他哺乳动物的发育障碍。哺乳动物杂种经常表现出来许多相同的胎盘生长异常，提高了复发的有趣可能性物种内部和物种之间的发育综合征可能反映了共同的破坏监管途径。但是，关于印迹的演变知之甚少监管网络，以及破坏基因组印记的贡献物种之间的生殖屏障仍未解决。拟议的研究将开始通过产生新的比较基因组数据来克服知识中这些基本差距关于胎盘基因表达和紧密相关的物种之间的基因组印记相互杂种。具体目的1和2将使用一系列混合啮齿动物系统生成全基因组胎盘转录，DNA甲基化和染色质结构的地图集遍布五种啮齿动物的五种和两个主要谱系（房屋小鼠和矮人仓鼠）。这些空前的比较数据将使我们能够解决基本的表观遗传机制控制基因组印记并量化胎盘表达和印迹如何具有发展了超过3000万年的分歧。特定目标3将使用系统遗传学检查杂交过度生长，胎盘表达和的遗传结构的方法矮人仓鼠和老鼠印迹。这些实验将使我们能够理解一种常见的胎盘发育不良形式的机械和遗传基础，并测试新的假设X染色体在调节烙印常染色体中起着核心作用监管网络。该研究计划的长期目标是（1）阐明基本控制基因组印迹的表观遗传机制（2）提供了对进化的见解印迹和胎盘表达的其他方面的节奏和理论驱动器，（3）测试关于破坏印迹和异常胎盘的因果关系的假设开发，（4）了解印迹表达网络的组织和演变，（5）将这些概念上的进步联系起来，以了解基因组印记的贡献生物多样性的起源。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Molecular Evolution of Ecological Specialisation: Genomic Insights from the Diversification of Murine Rodents.

DOI：
10.1093/gbe/evab103
发表时间：
2021-07-06
期刊：
Genome biology and evolution
影响因子：
3.3
作者：
Roycroft E;Achmadi A;Callahan CM;Esselstyn JA;Good JM;Moussalli A;Rowe KC
通讯作者：
Rowe KC

A natural variation-based screen in mouse cells reveals USF2 as a regulator of the DNA damage response and cellular senescence.

DOI：
10.1093/g3journal/jkad091
发表时间：
2023-07-05
期刊：
G3 (Bethesda, Md.)
影响因子：
0
作者：
通讯作者：

Automated Nuclear Cartography Reveals Conserved Sperm Chromosome Territory Localization across 2 Million Years of Mouse Evolution.

自动核制图揭示了 200 万年小鼠进化过程中保守的精子染色体区域定位。

DOI：
10.3390/genes10020109
发表时间：
2019
期刊：
Genes
影响因子：
3.5
作者：
Skinner,BenjaminMatthew;Bacon,Joanne;Rathje,ClaudiaCattoni;Larson,EricaLee;Kopania,EmilyEmikoKonishi;Good,JeffreyMartin;Affara,NabeelAhmed;Ellis,PeterJamesIvor
通讯作者：
Ellis,PeterJamesIvor

Molecular Evolution across Mouse Spermatogenesis.

DOI：
10.1093/molbev/msac023
发表时间：
2022-02-03
期刊：
Molecular biology and evolution
影响因子：
10.7
作者：
Kopania EEK;Larson EL;Callahan C;Keeble S;Good JM
通讯作者：
Good JM

Adaptive structural and functional evolution of the placenta protects fetal growth in high-elevation deer mice.

DOI：
10.1073/pnas.2218049120
发表时间：
2023-06-20
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子：
11.1
作者：
Wilsterman, Kathryn;Moore, Emily C.;Schweizer, Rena M.;Cunningham, Kirksey;Good, Jeffrey M.;Cheviron, Zachary A.
通讯作者：
Cheviron, Zachary A.