bromodomain

Publication Title: 
Epigenetics

Epigenetic proteins have recently emerged as novel anticancer targets. Among these, bromodomain and extra terminal domain (BET) proteins recognize lysine-acetylated histones, thereby regulating gene expression. Newly described small molecules that inhibit BET proteins BRD2, BRD3, and BRD4 reduce proliferation of NUT (nuclear protein in testis)-midline carcinoma, multiple myeloma, and leukemia cells in vitro and in vivo. These findings prompted us to determine whether BET proteins may be therapeutic targets in the most common primary adult brain tumor, glioblastoma (GBM).

Author(s): 
Pastori, Chiara
Daniel, Mark
Penas, Clara
Volmar, Claude-Henry
Johnstone, Andrea L.
Brothers, Shaun P.
Graham, Regina M.
Allen, Bryce
Sarkaria, Jann N.
Komotar, Ricardo J.
Wahlestedt, Claes
Ayad, Nagi G.
Publication Title: 
Oncotarget

Hormone-dependent gene expression requires dynamic and coordinated epigenetic changes. Estrogen receptor-positive (ER+) breast cancer is particularly dependent upon extensive chromatin remodeling and changes in histone modifications for the induction of hormone-responsive gene expression. Our previous studies established an important role of bromodomain-containing protein-4 (BRD4) in promoting estrogen-regulated transcription and proliferation of ER+ breast cancer cells.

Author(s): 
Nagarajan, Sankari
Benito, Eva
Fischer, Andre
Johnsen, Steven A.
Publication Title: 
Experimental Neurology

A hexanucleotide repeat expansion residing within the C9ORF72 gene represents the most common known cause of amyotrophic lateral sclerosis (ALS) and places the disease among a growing family of repeat expansion disorders. The presence of RNA foci, repeat-associated translation products, and sequestration of RNA binding proteins suggests that toxic RNA gain-of-function contributes to pathology while C9ORF72 haploinsufficiency may be an additional pathological factor.

Author(s): 
Zeier, Zane
Esanov, Rustam
Belle, Kinsley C.
Volmar, Claude-Henry
Johnstone, Andrea L.
Halley, Paul
DeRosa, Brooke A.
Khoury, Nathalie
van Blitterswijk, Marka
Rademakers, Rosa
Albert, Jeffrey
Brothers, Shaun P.
Wuu, Joanne
Dykxhoorn, Derek M.
Benatar, Michael
Wahlestedt, Claes
Publication Title: 
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience

Epigenetic processes that regulate histone acetylation play an essential role in behavioral and molecular responses to cocaine. To date, however, only a small fraction of the mechanisms involved in the addiction-associated acetylome have been investigated. Members of the bromodomain and extraterminal (BET) family of epigenetic "reader" proteins (BRD2, BRD3, BRD4, and BRDT) bind acetylated histones and serve as a scaffold for the recruitment of macromolecular complexes to modify chromatin accessibility and transcriptional activity.

Author(s): 
Sartor, Gregory C.
Powell, Samuel K.
Brothers, Shaun P.
Wahlestedt, Claes
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