Applications of CRISPR Genome Engineering in Cell Biology

Wang, Fangyuan; Qi, Lei S.

doi:10.1016/j.tcb.2016.08.004

Cited by 68 publications

(56 citation statements)

References 125 publications

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“…Moreover, since CRISPR/Cas9 technology can simultaneously activate or repress multiple genes in the same cell (Zalatan et al., 2015), it should be feasible to delete multiple methyltransferases using this approach to study the combined loss of histone modifications. Indeed, the CRISPR/Cas9 system has revolutionized cell biology research (Wang and Qi, 2016) and is likely to be useful for the study of HMTs. Such approaches will ultimately help decipher the complexity of combinatorial histone modifications and their contribution to tumorigenesis and guiding therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of histone methyltransferases in breast cancer – Opportunities for new targeted therapies?

Michalak

Visvader

2016

Molecular Oncology

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Histone methyltransferases (HMTs) catalyze the methylation of lysine and arginine residues on histone tails and non-histone targets. These important post-translational modifications are exquisitely regulated and affect chromatin compaction and transcriptional programs leading to diverse biological outcomes. There is accumulating evidence that genetic alterations of several HMTs impinge on oncogenic or tumor-suppressor functions and influence both cancer initiation and progression. HMTs therefore represent an opportunity for therapeutic targeting in those patients with tumors in which HMTs are dysregulated, to reverse the histone marks and transcriptional programs associated with aggressive tumor behavior. In this review, we describe the known histone methyltransferases and their emerging roles in breast cancer tumorigenesis.

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Section: Introductionmentioning

confidence: 99%

Dysregulation of histone methyltransferases in breast cancer – Opportunities for new targeted therapies?

Michalak

Visvader

2016

Molecular Oncology

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“…In this study, we generated, for the first time, CPI‐17 KO mice (CPI‐17 null ) using CRISPR/Cas9 (35). In KO# mice, CPI‐17 protein expression could not be detected in thoracic aorta either by Western blot or immunohistochemistry.…”

Section: Discussionmentioning

confidence: 99%

The essential role of phospho‐T38 CPI‐17 in the maintenance of physiological blood pressure using genetically modified mice

et al. 2018

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PKC-potentiated phosphorylation-dependent inhibitory protein of protein phosphatase 1 (CPI-17), an endogenous myosin phosphatase inhibitory protein, is considered a key molecule for Ca sensitization of the contractile apparatus. Here, we have used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 to generate CPI-17-deficient [knockout (KO)] and threonine 38 (T38)-phospho-resistant mice [threonine mutant into alanine (TA)], and then effects of CPI-17 on vascular contractility in vitro and mean blood pressure (MBP) in vivo were investigated. In isolated thoracic aorta, phorbol 12, 13-dibutyrate induced a sustained contraction of wild-type (WT) mice, whereas no contraction showed from TA or KO mice. A high concentration of KCl solution-induced contraction was not different between transgenic and WT mice. In contrast, phenylephrine (PE)-induced contractions in both mutant strains were significantly smaller than those of WT mice in association with a low level of myosin phosphorylation, suggesting that at least part of PE-induced contraction is regulated by phosphorylation of CPI-17 at T38. Finally, the physiologic role of CPI-17 in the regulation of blood pressure was investigated using radio telemetry. MBP was decreased significantly in both transgenic mice, even with a compensatory increase in heart rate. In summary, we generated KO and constitutively phospho-resistant mouse models of CPI-17 for the first time. p-CPI-17 at T38, possibly by PKC, could be important to maintain vascular contractility and blood pressure in vivo. -Yang, Q., Fujii, W., Kaji, N., Kakuta, S., Kada, K., Kuwahara, M., Tsubone, H., Ozaki, H., Hori, M. The essential role of phospho-T38 CPI-17 in the maintenance of physiological blood pressure using genetically modified mice.

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“…Beyond the use of chemical inhibitors or the testing of innovative anti-infective drugs, viral transformation (McBride et al 2000) allowing cell-specific functional analysis is a possible strategy. This can be combined with gene editing approaches such as the CRISPR-Cas9 system (Chen and Goncalves 2016;Wang and Qi 2016), thereby permitting mechanistic studies.…”

Section: Discussionmentioning

confidence: 99%

Human lung ex vivo infection models

2016

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Pneumonia is counted among the leading causes of death worldwide. Viruses, bacteria and pathogen-related molecules interact with cells present in the human alveolus by numerous, yet poorly understood ways. Traditional cell culture models little reflect the cellular composition, matrix complexity and three-dimensional architecture of the human lung. Integrative animal models suffer from species differences, which are of particular importance for the investigation of zoonotic lung diseases. The use of cultured ex vivo infected human lung tissue may overcome some of these limitations and complement traditional models. The present review gives an overview of common bacterial lung infections, such as pneumococcal infection and of widely neglected pathogens modeled in ex vivo infected lung tissue. The role of ex vivo infected lung tissue for the investigation of emerging viral zoonosis including influenza A virus and Middle East respiratory syndrome coronavirus is discussed. Finally, further directions for the elaboration of such models are revealed. Overall, the introduced models represent meaningful and robust methods to investigate principles of pathogen-host interaction in original human lung tissue.

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Applications of CRISPR Genome Engineering in Cell Biology

Cited by 68 publications

References 125 publications

Dysregulation of histone methyltransferases in breast cancer – Opportunities for new targeted therapies?

Dysregulation of histone methyltransferases in breast cancer – Opportunities for new targeted therapies?

The essential role of phospho‐T38 CPI‐17 in the maintenance of physiological blood pressure using genetically modified mice

Human lung ex vivo infection models

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