A CRISPR knockout screen identifies SETDB1-target retroelement silencing factors in embryonic stem cells [RESEARCH]
In mouse embryonic stem cells (mESCs), the expression of provirus and endogenous retroelements is epigenetically repressed. Although many cellular factors involved in retroelement silencing have been identified, the complete molecular mechanism remains elusive. In this study, we performed a genome-wide CRISPR screen to advance our understanding of retroelement silencing in mESCs. The Moloney murine leukemia virus (MLV)–based retroviral vector MSCV-GFP, which is repressed by the SETDB1/TRIM28 pathway in mESCs, was used as a reporter provirus, and we identified more than 80 genes involved in this process. In particular, ATF7IP and the BAF complex components are linked with the repression of most of the SETDB1 targets. We characterized two factors, MORC2A and RESF1, of which RESF1 is a novel molecule in retroelement silencing. Although both factors are recruited to repress provirus, their roles in repression are different. MORC2A appears to function dependent on repressive epigenetic modifications, while RESF1 regulates repressive epigenetic modifications associated with SETDB1. Our genome-wide CRISPR screen cataloged genes which function at different levels in silencing of SETDB1-target retroelements and provides a useful resource for further molecular studies.
We tested the proposal that medial temporal lobe (MTL) structures support not just memory but also high-level object perception. In one task, participants decided whether a line drawing could represent an object in three-dimensional space and, in another task, they saw the components of an ... more
Fear memory is a highly stable and durable form of memory, even over vast (remote) time frames. Nevertheless, some elements of fear memory can be forgotten, resulting in generalization. The purpose of this study is to determine how cued fear memory generalizes over time and measure underlyi ... more
A person sees an object once, and then seconds, minutes, hours, days, or weeks later, she sees it again. How is the person's visual memory for that object changed, improved, or degraded by the second encounter, compared to a situation in which she will have only seen the object once? The an ... more
Male breast cancer (MBC) is a very rare tumor type, occurring in just 1% of all breast cancer cases, and the underlying genetic causes and treatment of MBC is not well understood. In a paper researchers from Italy and the U.S. describe novel genetic variants found in a hormone receptor posi ... more
Huntington's disease is a neurodegenerative disorder characterized by huntingtin protein aggregates in a patient's brain, but how these aggregates form is not well understood. In a study published in Genome Research, researchers developed a novel computational strategy to identify interacti ... more
Pre-implantation genetic diagnosis (PGD) is used in fertility clinics to detect large chromosomal abnormalities or genetic mutations passed on by parents to their in vitro fertilized (IVF) embryos. However, it is not possible to comprehensively scan the embryo's genome to detect spontaneous ... more