Abstract:
:Ever since gene targeting or specific modification of genome sequences in mice was achieved in the early 1980s, the reverse genetic approach of precise editing of any genomic locus has greatly accelerated biomedical research and biotechnology development. In particular, the recent development of the CRISPR/Cas9 system has greatly expedited genetic dissection of three-dimensional (3D) genomes. CRISPR gene editing results from targeted genome cleavage by ectopic bacterial Cas9 nuclease followed by presumed random ligations via the host double-strand break (DSB) repair machineries. Recent studies revealed, however, that the CRISPR genome editing system is precise and predictable because of cohesive Cas9 cleavage of targeting DNA. Here, we synthesize the current understanding of CRISPR DNA fragment editing mechanisms and recent progress in predictable outcomes from precise genetic engineering of 3D genomes. Specifically, we first briefly describe historical genetic studies leading to CRISPR and 3D genome engineering. We then summarize different types of chromosomal rearrangements by DNA fragment editing. Finally, we review significant progress from precise one-dimensional (1D) gene editing toward predictable 3D genome engineering and synthetic biology. The exciting and rapid advances in this emerging field provide new opportunities and challenges to understand or digest 3D genomes.
journal_name
J Mol Cell Bioljournal_title
Journal of molecular cell biologyauthors
Wu Q,Shou Jdoi
10.1093/jmcb/mjaa060subject
Has Abstractpub_date
2020-10-30 00:00:00eissn
1674-2788issn
1759-4685pii
5943882pub_type
杂志文章abstract::Motile cilia and flagella are microtubule-based organelles important for cell locomotion and extracellular liquid flow through beating. Although axonenal dyneins that drive ciliary beat have been extensively studied in unicellular Chlamydomonas, to what extent such knowledge can be applied to vertebrate is poorly know...
journal_title:Journal of molecular cell biology
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abstract::Dying cells actively attract professional phagocytes by sending out soluble 'find-me' signals. The characterization and identification of the corresponding molecular entities have revealed that 'find-me' signals come in different flavors, including peptides, proteins, lipids and complex structures, such as apoptotic m...
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abstract::Extracellular vesicles (EVs) carry signals within or at their limiting membranes, providing a mechanism by which cells can exchange more complex information than what was previously thought. In addition to mRNAs and microRNAs, there are DNA fragments in EVs. Solexa sequencing indicated the presence of at least 16434 g...
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abstract::Cells encountering hypoxic stress conserve resources and energy by downregulating the protein synthesis. Here we demonstrate that one mechanism in this response is the translational repression of TOP mRNAs that encode components of the translational apparatus. This mode of regulation involves TSC and Rheb, as knockout...
journal_title:Journal of molecular cell biology
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abstract::Triple-negative breast cancer (TNBC), characterized by the lack of expression of the estrogen receptor, the progesterone receptor, and the human epidermal growth factor receptor 2, is an aggressive form of cancer that conveys unpredictable and poor prognosis due to limited treatment options and lack of effective targe...
journal_title:Journal of molecular cell biology
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abstract::Understanding the mechanism of how cholangiocytes (liver ductal cells) are activated upon liver injury and specified to hepatocytes would permit liver regenerative medicine. Here we achieved long-term in vitro expansion of mouse liver organoids by modulating signaling pathways with a combination of three small-molecul...
journal_title:Journal of molecular cell biology
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journal_title:Journal of molecular cell biology
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journal_title:Journal of molecular cell biology
pub_type: 杂志文章,评审
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更新日期:2011-06-01 00:00:00
abstract::Hematopoietic stem cells (HSCs) replenish all types of blood cells. It is debating whether HSCs in adults solely originate from the aorta-gonad-mesonephros (AGM) region, more specifically, the dorsal aorta, during embryogenesis. Here, we report that somite hematopoiesis, a previously unwitnessed hematopoiesis, can gen...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
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abstract::The mouse double minute 4 (MDM4) is emerging from the shadow of its more famous relative MDM2 and is starting to steal the limelight, largely due to its therapeutic possibilities. MDM4 is a vital regulator of the tumor suppressor p53. It restricts p53 transcriptional activity and also, at least in development, facilit...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章,评审
doi:10.1093/jmcb/mjz007
更新日期:2019-03-01 00:00:00
abstract::Breathing is an integrated motor behavior that is driven and controlled by a network of brainstem neurons. Zfhx4 is a zinc finger transcription factor and our results showed that it was specifically expressed in several regions of the mouse brainstem. Mice lacking Zfhx4 died shortly after birth from an apparent inabil...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjaa081
更新日期:2021-01-20 00:00:00
abstract::Scaffolding proteins play pivotal roles in the assembly of macromolecular machines such as the spliceosome. The adaptor protein CD2BP2, originally identified as a binding partner of the adhesion molecule CD2, is a pre-spliceosomal assembly factor that utilizes its glycine-tyrosine-phenylalanine (GYF) domain to co-loca...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjv039
更新日期:2015-10-01 00:00:00
abstract::Establishment of the primordial follicle (PF) pool is pivotal for the female reproductive lifespan; however, the mechanism of primordial folliculogenesis is poorly understood. Here, the transcription factor SP1 was shown to be essential for PF formation in mice. Our results showed that SP1 is present in both oocytes a...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjz059
更新日期:2020-04-24 00:00:00
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journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjaa033
更新日期:2020-07-08 00:00:00
abstract::Human colon carcinomas (CCs) represent a growing worldwide problem. One of the pathways that has been negatively implicated in the genesis of CCs is triggered by bone morphogenetic protein (BMP) ligands, which activate BMP receptors leading to the function of SMAD proteins in the nucleus. BMP signaling is altered in f...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjq035
更新日期:2010-12-01 00:00:00
abstract::Histone deacetylase 1 (HDAC1) is an essential epigenetic regulator belonging to a highly conserved family of deacetylases. Increased HDAC1 activity and expression often correlates with neoplastic transformation. Here we show how specific modification of HDAC1 by SUMO1, but not by SUMO2, facilitates HDAC1 degradation. ...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjt032
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pub_type: 杂志文章
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journal_title:Journal of molecular cell biology
pub_type: 杂志文章,评审
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journal_title:Journal of molecular cell biology
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journal_title:Journal of molecular cell biology
pub_type: 杂志文章
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更新日期:2019-09-19 00:00:00
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journal_title:Journal of molecular cell biology
pub_type: 杂志文章
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更新日期:2017-12-01 00:00:00
abstract::MEK inhibitor has been highlighted as a promising anti-tumor drug but its effect has been reported as varying over a wide range depending on patho-physiological conditions. In this study, we employed a systems approach by combining biochemical experimentation with in silico simulations to investigate the resistance me...
journal_title:Journal of molecular cell biology
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abstract::Mdm2 is the key negative regulator of the tumour suppressor p53, making it an attractive target for anti-cancer drug design. We recently identified a new role of Mdm2 in gene repression through its direct interaction with several proteins of the polycomb group (PcG) family. PcG proteins form polycomb repressive comple...
journal_title:Journal of molecular cell biology
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journal_title:Journal of molecular cell biology
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