The highly homologous
bromodomain containing protein 7 (BRD7) is a component of the SWI / SNF polybromo - associated BAF (PBAF) complex and has been proposed as a tumor suppressor [2].
The active component is a p300 / CBP
bromodomain inhibitor that has a profound effect on the drivers of CPRC.
BAZ2 - ICR did not show significant thermal shifts against all
other bromodomains, except for Cat Eye syndrome chromosome region, candidate 2 (CECR2), where a smaller but significant shift (ΔTm: 2.0 °C) was observed.
A study published by Cell Press August 1st in the journal Cell reveals the key role of a family of molecules known
as bromodomain and extraterminal domain (BET) proteins in activating genes that contribute to heart failure.
Discovered that BET
bromodomain epigenetic regulators function as critical drivers of heart failure pathogenesis and vascular injury responses that can be pharmacologically targeted in vivo
The Fluorescence Recovery After Photobleaching (FRAP) assay has been used to validate many of the SGC's chemical probes
against bromodomains.
To investigate whether BAZ2 - ICR can displace
BAZ2 bromodomains from chromatin in living cells, we performed a fluorescence recovery after photobleaching (FRAP) assay utilizing GFP - tagged BAZ2A full length protein transfected into human osteosarcoma cells (U2OS).
Brd4 forms complexes with chromatin via two
tandem bromodomains (BD1 and BD2) that bind to acetylated lysine residues in histones and Brd4 association with acetylated chromatin is believed to regulate the recruitment of elongation factor b and additional transcription factors to specific promoter regions.
The inhibitor was screened at 10 μM concentration against 47
bromodomains using a temperature shift assay.
A contract lab was able to verify a study he co-led with Constantine Mitsiades while at Dana - Farber Cancer Institute, testing an inhibitor of a class of proteins called
BET bromodomains.
«In this study we successfully targeted histone acetylation with
a bromodomain inhibitor, a compound that is currently in studies for different types of advanced cancers in adults, but has never been studied in DIPG,» said senior author Ali Shilatifard, PhD, Chair of Department of Biochemistry and Molecular Genetics and Robert Francis Furchgott Professor at Northwestern University Feinberg School of Medicine.
Chris Vakoc Chromatin; transcriptional regulation; acute myeloid leukemia; BET
bromodomains; lysine methyltransferases
Specifically, we have demonstrated that histone deacetylases (HDACs) and
bromodomain - containing proteins are required for colon cancer cell growth, and have demonstrated that inhibitors of these enzymes induce growth arrest and apoptosis in colon cancer cell lines.
The catalytic core of p300 shown here has a domain that acetylates chromatin (histone acetyltransferase or HAT) and a domain that recognizes the acetylation (
bromodomain or Bd).
Additionally, they showed that disrupting ENL led to anti-leukemic effects and exacerbated the sensitivity of leukemia cells to
bromodomain and extra-terminal (BET) inhibitors, thus setting the ground work for developing ENL inhibitors as potential therapeutics for AML.
Cells were transfected with GFP - tagged BAZ2A or BRD4 and treated with 1 μM PFI - 1 (a selective probe for BET
Bromodomains) or BAZ2 - ICR.
The bromodomain containing protein 9 (BRD9) has been reported as a component of the switch / sucrose non-fermentable (SWI / SNF) brahma - related gene 1 - associated factor (BAF) complex, which plays a key role in chromatin remodelling and transcription control [1] although the precise biological role is unknown.
Proteins of the BAZ (
bromodomain adjacent zinc finger) family are characterized by a carboxy - terminal bromodomain adjacent to a PHD finger and a WACZ motif.
It was previously thought the only readers of acetyl groups were
bromodomains.
(+ / --RRB-- JQ1 -LRB-(+ / --RRB- SGCBD01) is a selective BET
bromodomain (BRD) inhibitor that inhibits Brd4 (Bromodomain - containing 4).
Bromodomains have long been a target of cancer therapuetic development, and the YEATS domain may now provide a new avenue for the development of future therapeutic targets.
These drugs act by inhibiting a protein called BRD4, a member of a family of proteins called BET
bromodomains, which directly influences heart failure.
Haldar discovered that stress triggers the activity of another important family of cardiac proteins called BET
bromodomains.
While it is extremely difficult to target proteins like TBX5 and GATA4 with a drug, BET
bromodomains can be targeted safely.
We found that treatment of human multiple myeloma (MM) cells with the small - molecular inhibitor of BET
bromodomains, (+)- JQ1, selectively downregulated MYC transcription, which is similar to what was reported in the original study (Figure 3B; Delmore et al., 2011).