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The essential Sth1p is the protein most closely related to the conserved Snf2p/Swi2p in Saccharomyces cerevisiae. Sth1p purified from yeast has a DNA-stimulated ATPase activity required for its function in vivo. The finding that Sth1p is a component of a multiprotein complex capable of ATP-dependent remodeling of the structure of chromatin (RSC) in vitro,(More)
Previous studies have identified single amino acid changes within either histone H3 or H4 (Sin- versions) that allow transcription in the absence of the yeast SWI-SNF complex. The histone H4 mutants are competent for nucleosome assembly in vivo, and the residues that are altered appear to define a discrete domain on the surface of the histone octamer. We(More)
Heterochromatin protein 1 Hsalpha (HP1(Hsalpha)) is one of three human proteins that share sequence similarity with Drosophila HP1. HP1 proteins are enriched at centric heterochromatin and play a role in chromatin packaging and gene regulation. In humans, HP1(Hsalpha) is down-regulated in highly invasive/metastatic breast cancer cells, compared to poorly(More)
Glioblastoma remains one of the most lethal types of cancer, and is the most common brain tumour in adults. In particular, tumour recurrence after surgical resection and radiation invariably occurs regardless of aggressive chemotherapy. Here, we provide evidence that the transcription factor ZEB1 (zinc finger E-box binding homeobox 1) exerts simultaneous(More)
Chromatin creates transcriptional barriers that are overcome by coactivator activities such as histone acetylation by Gcn5 and ATP-dependent chromatin remodeling by SWI/SNF. Factors defining the differential coactivator requirements in the transactivation of various promoters remain elusive. Induction of the Saccharomyces cerevisiae PHO5 promoter does not(More)
Approximately 800 transcripts in Saccharomyces cerevisiae are cell cycle regulated. The oscillation of approximately 40% of these genes, including a prominent subclass involved in nutrient acquisition, is not understood. To address this problem, we focus on the mitosis-specific activation of the phosphate-responsive promoter, PHO5. We show that the(More)
Human tumors are comprised of heterogeneous cell populations that display diverse molecular and phenotypic features. To examine the extent to which epigenetic differences contribute to intratumoral cellular heterogeneity, we have developed a high-throughput method, termed MAPit-patch. The method uses multiplexed amplification of targeted sequences from(More)
Post-translational modifications of histone amino-terminal tails are a key determinant in gene expression. Histone methylation plays a dual role in gene regulation. Methylation of lysine 9 of histone H3 in higher eukaryotes is associated with transcriptionally inactive heterochromatin, whereas H3 lysine 4 methylation correlates with active chromatin.(More)
17Beta-estradiol (E2) induced c-fos protooncogene mRNA levels in MCF-7 human breast cancer cells, and maximal induction was observed within 1 h after treatment. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) inhibited the E2-induced response within 2 h. The molecular mechanism of this response was further investigated using pFC2-CAT, a construct containing a(More)
Genome-scale mapping suggests that the function of DNA methylation varies with genomic context beyond transcriptional repression. However, the use of DNA-demethylating agents (e.g. 5-aza-2'-deoxycytidine (5aza-dC)) to study epigenetic regulation often focuses on gene activation and ignores repression elicited by 5aza-dC. Here, we show that repression of(More)