scholarly journals Super elongation complex promotes early HIV transcription and its function is modulated by P-TEFb

Transcription ◽  
2017 ◽  
Vol 8 (3) ◽  
pp. 133-149 ◽  
Author(s):  
Alona Kuzmina ◽  
Simona Krasnopolsky ◽  
Ran Taube
Keyword(s):  
Elongation Complex ◽  
Hiv Transcription ◽  
Super Elongation Complex

scholarly journals Competition between PAF1 and MLL1/COMPASS confers the opposing function of LEDGF/p75 in HIV latency and proviral reactivation

2020 ◽  
Vol 6 (20) ◽  
pp. eaaz8411
Author(s):  
Ru Gao ◽  
Jiaqian Bao ◽  
Han Yan ◽  
Liya Xie ◽  
Wanchang Qin ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Therapeutic Potential ◽  
Life Cycles ◽  
Elongation Complex ◽  
Hiv Transcription ◽  
Super Elongation Complex ◽  
Replication Control ◽  
Regulatory Functions ◽  
Transcriptional Reactivation ◽  
Hiv Integration

Transcriptional status determines the HIV replicative state in infected patients. However, the transcriptional mechanisms for proviral replication control remain unclear. In this study, we show that, apart from its function in HIV integration, LEDGF/p75 differentially regulates HIV transcription in latency and proviral reactivation. During latency, LEDGF/p75 suppresses proviral transcription via promoter-proximal pausing of RNA polymerase II (Pol II) by recruiting PAF1 complex to the provirus. Following latency reversal, MLL1 complex competitively displaces PAF1 from the provirus through casein kinase II (CKII)–dependent association with LEDGF/p75. Depleting or pharmacologically inhibiting CKII prevents PAF1 dissociation and abrogates the recruitment of both MLL1 and Super Elongation Complex (SEC) to the provirus, thereby impairing transcriptional reactivation for latency reversal. These findings, therefore, provide a mechanistic understanding of how LEDGF/p75 coordinates its distinct regulatory functions at different stages of the post-integrated HIV life cycles. Targeting these mechanisms may have a therapeutic potential to eradicate HIV infection.

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.

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