An increasing number of transcription factors have been shown to activate DNA replication. However, the underlying mechanism remains to be elucidated. Here it is shown that when tethered to a cellular replication origin, the acidic transcriptional activation domain of the breast cancer protein BRCA1 alters the local chromatin structure and stimulates chromosomal DNA replication. Cancer-predispo...

Metabolic diseases result from multiple genetic and environmental factors. We report here that one manner in which environmental factors can contribute to metabolic disease progression is through modification to chromatin. We demonstrate that high fat diet leads to chromatin remodeling in the livers of C57BL/6J mice, as compared with mice fed a control diet, and that these chromatin changes are...

Chromatin remodeling and protein acetylation control gene expression and consequently regulate cellular growth and differentiation. Here we review the role of individual chromatin remodeling factors, acetyltransferases and deacetylases in the establishment and maintenance of different cell lineages and in the genesis of some human diseases.

The ISWI class of chromatin remodeling factors exhibits potent chromatin remodeling activities in vitro. However, the in vivo functions of this class of factors are unknown at a molecular level. We have found that S. cerevisiae Isw2 complex represses transcription of early meiotic genes during mitotic growth in a parallel pathway to Rpd3-Sin3 histone deacetylase complex. This repressor function...

Nucleotide excision repair (NER) is an important DNA repair mechanism required for cellular resistance against UV light and toxic chemicals such as those found in tobacco smoke. In living cells, NER efficiently detects and removes DNA lesions within the large nuclear macromolecular complex called chromatin. The condensed nature of chromatin inhibits many DNA metabolizing activities, including N...

Progesterone receptor (PR), a member of the nuclear receptor superfamily, is a key regulator of several processes in reproductive function. We have studied the dynamics of the interaction of PR with a natural target promoter in living cells through the use of fluorescence recovery after photobleaching (FRAP) analysis and also have characterized the dynamics of the interaction of PR with the mou...

The eukaryotic genome is packaged as chromatin with nucleosomes comprising its basic structural unit, but the detailed structure of chromatin and its dynamic remodeling in terms of individual nucleosome positions has not been completely defined experimentally for any genome. We used ultra-high-throughput sequencing to map the remodeling of individual nucleosomes throughout the yeast genome befo...

The INO80 and SWR1 complexes belong to the INO80 subfamily of ATP-dependent chromatin-remodeling complexes. These complexes interact with nucleosomes and remodel chromatin by either sliding nucleosomes along the DNA or exchanging histones within nucleosomes. In doing so, the INO80 and SWR1 complexes promote recruitment of regulatory factors to DNA. Distinct from other subfamilies of chromatin-r...

The interplay between different levels of gene regulation in modulating developmental transcriptional programs, such as histonemodifications and chromatin remodeling, is not well understood. Here, we show that the chromatin remodeling factor Brg1 is required for enhancer activation in mesoderm induction. In an embryonic stem cell-based directed differentiation assay, the absence of Brg1 results...

The molecular carcinogenesis of intraductal tubulopapillary neoplasms (ITPN), recently described as rare in the pancreato-biliary tract with a favorable prognosis despite high incidence associated adenocarcinoma, is still poorly understood. To identify driver genes, chromosomal gains and losses, mutational signatures, key signaling pathways, potential therapeutic targets, profile 11 biliary 6 p...