Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells
نویسندگان
چکیده
Characterizing the multifaceted contribution of genetic and epigenetic factors to disease phenotypes is a major challenge in human genetics and medicine. We carried out high-resolution genetic, epigenetic, and transcriptomic profiling in three major human immune cell types (CD14+ monocytes, CD16+ neutrophils, and naive CD4+ T cells) from up to 197 individuals. We assess, quantitatively, the relative contribution of cis-genetic and epigenetic factors to transcription and evaluate their impact as potential sources of confounding in epigenome-wide association studies. Further, we characterize highly coordinated genetic effects on gene expression, methylation, and histone variation through quantitative trait locus (QTL) mapping and allele-specific (AS) analyses. Finally, we demonstrate colocalization of molecular trait QTLs at 345 unique immune disease loci. This expansive, high-resolution atlas of multi-omics changes yields insights into cell-type-specific correlation between diverse genomic inputs, more generalizable correlations between these inputs, and defines molecular events that may underpin complex disease risk.
منابع مشابه
HDAC Inhibitors and Heat Shock Proteins (Hsps)
Epigenetic alterations, including DNA acetylation, hypermethylation and hypomethylation, and the associated transcriptional changes of the affected genes are central to the evolution and progression of various human cancers, including pancreatic cancer. Cancer-associated epigenetic alterations are attractive therapeutic targets because such epigenetic alterations, unlike genetic changes, are po...
متن کاملP-88: Comparing Epigenetic Profile of Oct4 Regulatory Region in Embryonal Carcinoma Cells under Retinoic Acid Induction
Background: Embryonal carcinoma (EC) cells derived from germ cell tumors are valuable tools for investigating differentiation and developmental biology processes in vitro. The advantage of the reproducible and rapid expansion of these cell lines provides a useful alternative to embryos for the study of mammalian cell differentiation. During early stages of cell differentiation, the rate of tran...
متن کاملI-13: Transcriptome Dynamics of Human and Mouse Preimplantation Embryos Revealed by Single Cell RNA-Sequencing
Background: Mammalian preimplantation development is a complex process involving dramatic changes in the transcriptional architecture. However, it is still unclear about the crucial transcriptional network and key hub genes that regulate the proceeding of preimplantation embryos. Materials and Methods: Through single-cell RNAsequencing (RNA-seq) of both human and mouse preimplantation embryos, ...
متن کاملThe function of epigenetic processes in multiple sclerosis: review article
Multiple Sclerosis (MS) is a chronic neurological and inflammatory disorder that affects the nervous system. The etiology of MS is unknown, but genetic and environmental factors are involved in its pathogenesis. There is increasing evidence suggesting the role of epigenetic mechanisms in the pathogenesis of multiple sclerosis. Lack of vitamin D, smoking, and Epstein barr virus can cause epigene...
متن کاملGenetic and Epigenetic landscape of Germline Stem Cells
Elucidating the critical epigenetics events involved in differentiation and reprogramming of cells to primordial germ cells (PGCs) is among the interesting issues in stem cell research. Here, I will talk about critical transcription factors and global hypomethylation in development of germ cells. Evidence strongly suggests that the earliest PGCs emerging in the E7.25 mouse embryo epiblast have...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 167 شماره
صفحات -
تاریخ انتشار 2016