scholarly journals Super Elongation Complex as a Targetable Dependency in Diffuse Midline Glioma

Cell Reports ◽  
2020 ◽  
Vol 31 (1) ◽  
pp. 107485 ◽  
Author(s):  
Nathan A. Dahl ◽  
Etienne Danis ◽  
Ilango Balakrishnan ◽  
Dong Wang ◽  
Angela Pierce ◽  
...  
Keyword(s):  
Elongation Complex ◽  
Super Elongation Complex ◽  
Diffuse Midline Glioma

Allosteric transcription stimulation by RNA polymerase II super elongation complex

2021 ◽  
Author(s):  
Ying Chen ◽  
Seychelle M. Vos ◽  
Christian Dienemann ◽  
Momchil Ninov ◽  
Henning Urlaub ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Elongation Complex ◽  
Super Elongation Complex

scholarly journals DIPG-10. THE ONCOGENIC ROLE OF THE SUPER ELONGATION COMPLEX IN H3K27M-MUTANT DIFFUSE MIDLINE GLIOMAS

2018 ◽  
Vol 20 (suppl_2) ◽  
pp. i50-i50
Author(s):  
Nathan A Dahl ◽  
Sujatha Venkataraman ◽  
Ilango Balakrishnan ◽  
Krishna Madhavan ◽  
Susan Fosmire ◽  
...  
Keyword(s):  
Elongation Complex ◽  
Super Elongation Complex

scholarly journals P-TEFb, the Super Elongation Complex and Mediator Regulate a Subset of Non-paused Genes during Early Drosophila Embryo Development

PLoS Genetics ◽  
2015 ◽  
Vol 11 (2) ◽  
pp. e1004971 ◽  
Author(s):  
Olle Dahlberg ◽  
Olga Shilkova ◽  
Min Tang ◽  
Per-Henrik Holmqvist ◽  
Mattias Mannervik
Keyword(s):  
Embryo Development ◽  
Drosophila Embryo ◽  
Elongation Complex ◽  
Super Elongation Complex ◽  
Early Drosophila Embryo

scholarly journals Super elongation complex contains a TFIIF-related subcomplex

Transcription ◽  
2016 ◽  
Vol 7 (4) ◽  
pp. 133-140 ◽  
Author(s):  
Bruce A. Knutson ◽  
Marissa L. Smith ◽  
Nancy Walker-Kopp ◽  
Xia Xu
Keyword(s):  
Elongation Complex ◽  
Super Elongation Complex

scholarly journals Transcriptional Elongation Control of Hepatitis B Virus Covalently Closed Circular DNA Transcription by Super Elongation Complex and BRD4

2017 ◽  
Vol 37 (19) ◽  
Author(s):  
Joel Celio Francisco ◽  
Qian Dai ◽  
Zhuojuan Luo ◽  
Yan Wang ◽  
Roxanne Hui-Heng Chong ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Intermediate Step ◽  
Hbv Reactivation ◽  
Transcriptional Elongation ◽  
Elongation Complex ◽  
Super Elongation Complex ◽  
Chronic Hepatitis B Virus ◽  
B Virus

ABSTRACT Chronic hepatitis B virus (HBV) infection can lead to liver cirrhosis and hepatocellular carcinoma. HBV reactivation during or after chemotherapy is a potentially fatal complication for cancer patients with chronic HBV infection. Transcription of HBV is a critical intermediate step of the HBV life cycle. However, factors controlling HBV transcription remain largely unknown. Here, we found that different P-TEFb complexes are involved in the transcription of the HBV viral genome. Both BRD4 and the super elongation complex (SEC) bind to the HBV genome. The treatment of bromodomain inhibitor JQ1 stimulates HBV transcription and increases the occupancy of BRD4 on the HBV genome, suggesting the bromodomain-independent recruitment of BRD4 to the HBV genome. JQ1 also leads to the increased binding of SEC to the HBV genome, and SEC is required for JQ1-induced HBV transcription. These findings reveal a novel mechanism by which the HBV genome hijacks the host P-TEFb-containing complexes to promote its own transcription. Our findings also point out an important clinical implication, that is, the potential risk of HBV reactivation during therapy with a BRD4 inhibitor, such as JQ1 or its analogues, which are a potential treatment for acute myeloid leukemia.

scholarly journals Super elongation complex as a targetable dependency in diffuse midline glioma

2020 ◽  
Author(s):  
Nathan A. Dahl ◽  
Etienne Danis ◽  
Ilango Balakrishnan ◽  
Dong Wang ◽  
Angela Pierce ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Elongation Complex ◽  
Curative Therapy ◽  
Super Elongation Complex ◽  
Small Molecule Inhibition ◽  
Promising Therapeutic Approach ◽  
Clonogenic Potential ◽  
Diffuse Intrinsic Pontine Gliomas ◽  
Shrna Screen

AbstractMutations in the histone 3 gene (H3K27M) are the eponymous drivers in diffuse intrinsic pontine gliomas (DIPGs) and other diffuse midline gliomas (DMGs), aggressive pediatric brain cancers for which no curative therapy currently exists. The salient molecular consequence of these recurrent oncohistones is a global loss of repressive H3K27me3 residues and broad epigenetic dysregulation. In order to identify specific, therapeutically targetable epigenetic dependencies within this disease context, we performed an shRNA screen targeting 408 genes classified as epigenetic/chromatin-associated molecules in patient-derived DMG cultures. This approach identified AFF4, the scaffold protein of the super elongation complex (SEC), as a previously-undescribed dependency in DMG. Interrogation of SEC function demonstrated a key role for maintaining DMG cell viability and clonogenic potential while promoting self-renewal of DMG tumor stem cells. Small-molecule inhibition of the SEC with the highly-specific, clinically relevant CDK9 inhibitors atuveciclib and AZD4573 restores regulatory RNA polymerase II pausing, promotes cellular differentiation, and leads to potent anti-tumor effect both in vitro and in patient-derived xenograft models. These studies present a biologic rationale for translational exploration of CDK9 inhibition as a promising therapeutic approach in a disease which currently has no effective medical therapies.

scholarly journals ENL initiates multivalent phase separation of the super elongation complex (SEC) in controlling rapid transcriptional activation

2020 ◽  
Vol 6 (14) ◽  
pp. eaay4858 ◽  
Author(s):  
Chenghao Guo ◽  
Zhuanzhuan Che ◽  
Junjie Yue ◽  
Peng Xie ◽  
Shaohua Hao ◽  
...  
Keyword(s):  
Phase Separation ◽  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Liquid Droplet ◽  
Critical Role ◽  
Elongation Factor ◽  
Elongation Complex ◽  
Intrinsically Disordered ◽  
Super Elongation Complex

Release of paused RNA polymerase II (Pol II) requires incorporation of the positive transcription elongation factor b (P-TEFb) into the super elongation complex (SEC), thus resulting in rapid yet synchronous transcriptional activation. However, the mechanism underlying dynamic transition of P-TEFb from inactive to active state remains unclear. Here, we found that the SEC components are able to compartmentalize and concentrate P-TEFb via liquid-liquid phase separation from the soluble inactive HEXIM1 containing the P-TEFb complex. Specifically, ENL or its intrinsically disordered region is sufficient to initiate the liquid droplet formation of SEC. AFF4 functions together with ENL in fluidizing SEC droplets. SEC droplets are fast and dynamically formed upon serum exposure and required for rapid transcriptional induction. We also found that the fusion of ENL with MLL can boost SEC phase separation. In summary, our results suggest a critical role of multivalent phase separation of SEC in controlling transcriptional pause release.

Sign in / Sign up

Export Citation Format

Share Document