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Androgen receptor (AR) is required for sexual differentiation and is implicated in the development of prostate cancer. Here we describe distinct functions for cofactor proteins and gene regulatory elements in the assembly of AR-mediated transcription complexes. The formation of an activation complex involves AR, coactivators, and RNA polymerase II(More)
Many cofactors bind the hormone-activated estrogen receptor (ER), yet the specific regulators of endogenous ER-mediated gene transcription are unknown. Using chromatin immunoprecipitation (ChIP), we find that ER and a number of coactivators rapidly associate with estrogen responsive promoters following estrogen treatment in a cyclic fashion that is not(More)
Selective estrogen receptor modulators (SERMs) mimic estrogen action in certain tissues while opposing it in others. The therapeutic effectiveness of SERMs such as tamoxifen and raloxifene in breast cancer depends on their antiestrogenic activity. In the uterus, however, tamoxifen is estrogenic. Here, we show that both tamoxifen and raloxifene induce the(More)
Lysine-specific demethylase 1 (LSD1) exerts pathway-specific activity in animal development and has been linked to several high-risk cancers. Here, we report that LSD1 is an integral component of the Mi-2/nucleosome remodeling and deacetylase (NuRD) complex. Transcriptional target analysis revealed that the LSD1/NuRD complexes regulate several cellular(More)
In this study, we show that HuR destabilizes p16 INK4 mRNA. Although the knockdown of HuR or AUF1 increased p16 expression, concomitant AUF1 and HuR knockdown had a much weaker effect. The knockdown of Ago2, a component of the RNA-induced silencing complex (RISC), stabilized p16 mRNA. The knockdown of HuR diminished the association of the p16 3؅(More)
Dendritic arborization is one of the key determinants of precise circuits for information processing in neurons. Unraveling the molecular mechanisms underlying dendrite morphogenesis is critical to understanding the establishment of neuronal connections. Here, using gain- and loss-of-function approaches, we defined the chromodomain protein and transcription(More)
Tamoxifen, a selective oestrogen receptor modulator, has been used in the treatment of all stages of hormone-responsive breast cancer. However, tamoxifen shows partial oestrogenic activity in the uterus and its use has been associated with an increased incidence of endometrial cancer. The molecular explanation for these observations is not known. Here we(More)
Jumonji domain-containing 6 (JMJD6) is a member of the Jumonji C domain-containing family of proteins. Compared to other members of the family, the cellular activity of JMJD6 is still not clearly defined and its biological function is still largely unexplored. Here we report that JMJD6 is physically associated with the tumor suppressor p53. We demonstrated(More)
Hydroxyurea, a well-known DNA replication inhibitor, induces cell cycle arrest and intact checkpoint functions are required to survive DNA replication stress induced by this genotoxic agent. Perturbed DNA synthesis also results in elevated levels of DNA damage. It is unclear how organisms prevent accumulation of this type of DNA damage that coincides with(More)
The origin of new exons is an important mechanism for proteome diversity. Here, we report the recurrent origination of new exons in mammalian chromodomain Y-like (CDYL) genes and the functional consequences associated with the acquisition of the new exons. Driven by positive selection, the newly evolved longer peptide exhibits weaker transcription(More)