Anna C. Groner
ETH Zurich
GeneCancerCorepressorRepressorRegulation of gene expressionSPOPAndrogenTRIM24Prostate cancerEpigeneticsCancer researchGeneticsBioinformaticsAndrogen receptorHistoneBromodomainChromatinTranscription factorBiologyCell biology
23Publications
16H-index
2,167Citations
Publications 21
Newest
#1Laura Cato (Harvard University)H-Index: 9
#2Jonas de Tribolet-Hardy (ETH Zurich)H-Index: 3
Last. Myles Brown (Harvard University)H-Index: 113
view all 35 authors...
Summary Androgen deprivation therapy for prostate cancer (PCa) benefits patients with early disease, but becomes ineffective as PCa progresses to a castration-resistant state (CRPC). Initially CRPC remains dependent on androgen receptor (AR) signaling, often through increased expression of full-length AR (ARfl) or expression of dominantly active splice variants such as ARv7. We show in ARv7-dependent CRPC models that ARv7 binds together with ARfl to repress transcription of a set of growth-suppr...
55 CitationsSource
: Steroid hormones mediate critical lineage-specific developmental and physiologic responses. They function by binding their cognate receptors, which are transcription factors that drive specific gene expression programs. The requirement of most prostate cancers for androgen and most breast cancers for estrogen has led to the development of endocrine therapies that block the action of these hormones in these tumors. While initial endocrine interventions are successful, resistance to therapy ofte...
25 CitationsSource
#1K. M. A. Dreijerink (Harvard University)H-Index: 4
#1Koen M.A. Dreijerink (Harvard University)H-Index: 21
Last. Myles Brown (Harvard University)H-Index: 113
view all 14 authors...
While the multiple endocrine neoplasia type 1 (MEN1) gene functions as a tumor suppressor in a variety of cancer types, we explored its oncogenic role in breast tumorigenesis. The MEN1 gene product menin is involved in H3K4 trimethylation and co-activates transcription. We integrated ChIP-seq and RNA-seq data to identify menin target genes. Our analysis revealed that menin-dependent target gene promoters display looping to distal enhancers that are bound by menin, FOXA1 and GATA3. In this fashio...
25 CitationsSource
#1Anna C. Groner (Harvard University)H-Index: 16
#2Myles Brown (Harvard University)H-Index: 113
Last. Jean-Philippe TheurillatH-Index: 15
view all 3 authors...
3 CitationsSource
#1Anna C. Groner (Harvard University)H-Index: 16
#2Laura Cato (Harvard University)H-Index: 9
Last. Myles Brown (Harvard University)H-Index: 113
view all 13 authors...
Androgen receptor (AR) signaling is a key driver of prostate cancer (PC). While androgen-deprivation therapy is transiently effective in advanced disease, tumors often progress to a lethal castration-resistant state (CRPC). We show that recurrent PC-driver mutations in SPOP stabilize the TRIM24 protein, which promotes proliferation under low androgen conditions. TRIM24 augments AR signaling, and AR and TRIM24 co-activated genes are significantly up-regulated in CRPC. Expression of TRIM24 protein...
1 CitationsSource
#1Jennifer M. Spangle (Harvard University)H-Index: 11
#2K. M. A. Dreijerink (Harvard University)H-Index: 4
Last. Myles Brown (Harvard University)H-Index: 113
view all 11 authors...
Post-translational histone H3 modifications regulate transcriptional competence. The mechanisms by which the epigenome is regulated in response to oncogenic signaling remain unclear. Here we show that H3K4me3 is increased in breast tumors driven by an activated PIK3CA allele and that inhibition of PI3K/AKT signaling reduces promoter-associated H3K4me3 in human breast cancer cells. We show that the H3K4 demethylase KDM5A is an AKT target and that phosphorylation of KDM5A regulates its nuclear loc...
46 CitationsSource
#1Anna C. Groner (Harvard University)H-Index: 16
#2Laura Cato (Harvard University)H-Index: 9
Last. Myles Brown (Harvard University)H-Index: 113
view all 22 authors...
Androgen receptor (AR) signaling is a key driver of prostate cancer (PC). While androgen-deprivation therapy is transiently effective in advanced disease, tumors often progress to a lethal castration-resistant state (CRPC). We show that recurrent PC-driver mutations in speckle-type POZ protein (SPOP) stabilize the TRIM24 protein, which promotes proliferation under low androgen conditions. TRIM24 augments AR signaling, and AR and TRIM24 co-activated genes are significantly upregulated in CRPC. Ex...
117 CitationsSource
#1Anna C. GronerH-Index: 16
Last. Myles BrownH-Index: 113
view all 5 authors...
Source
#1Jens-Erik Dietrich (EMBL-EBI: European Bioinformatics Institute)H-Index: 9
#2Laura Panavaite (EMBL-EBI: European Bioinformatics Institute)H-Index: 2
Last. Takashi Hiiragi (EMBL-EBI: European Bioinformatics Institute)H-Index: 25
view all 10 authors...
Mammalian development begins with the segregation of embryonic and extra-embryonic lineages in the blastocyst. Recent studies revealed cell-to-cell gene expression heterogeneity and dynamic cell rearrangements during mouse blastocyst formation. Thus, mechanistic understanding of lineage specification requires quantitative description of gene expression dynamics at a single-cell resolution in living embryos. However, only a few fluorescent gene expression reporter mice are available and quantitat...
22 CitationsSource
#1Patrick Tschopp (Harvard University)H-Index: 14
#2Emma Sherratt (Harvard University)H-Index: 20
Last. Clifford J. Tabin (Harvard University)H-Index: 119
view all 9 authors...
It has been known for some time that limbs share at least some of their molecular patterning mechanism with external genitalia; here, this connection is examined in a variety of species, revealing that once-shared developmental trajectories could help to explain the observed patterning similarities.
56 CitationsSource