Biomedical subjects

Masaya Oki

Publications and source records attributed to Masaya Oki.

4 recordsLinked to original sources

PubMed2006

H2A.Z functions to regulate progression through the cell cycle.

Histone H2A variants are highly conserved proteins found ubiquitously in nature and thought to perform specialized functions in the cell. Studies in yeast on the histone H2A variant H2A.Z have shown a role for this protein in transcription as well as chromosome segregation. Our studies have focused on understanding the role of H2A.Z during cell cycle progression. We found that htz1delta cells were delayed in DNA replication and progression through the cell cycle. Furthermore, cells lacking H2A.Z required the S-phase checkpoint pathway for survival. We also found that H2A.Z localized to the promoters of cyclin genes, and cells lacking H2A.Z were delayed in the induction of these cyclin genes. Several different models are proposed to explain these observations.

Cell Cycle↗

PubMed2005

Barrier function at HMR.

The silenced HMR domain is restricted from spreading by barrier elements, and the right barrier is a unique t-RNA(THR) gene. We show that sequences immediately flanking the silenced domain were enriched in acetylated, but not methylated, histones, whereas the barrier element was associated with a nucleosome-free region. Surprisingly, the SAGA acetyltransferase resided across the entire region. We further demonstrate that a mutation in the barrier eliminated the nucleosome-free gap but only subtly altered the distribution of SAGA. Interestingly, neither reformation of the nucleosome nor mutations in chromatin-modifying enzymes alone led to an unrestricted spread of silenced chromatin. Double mutations in the t-RNA barrier and these complexes, on the other hand, led to a significant spread of Sir proteins. These results suggest two overlapping mechanisms function to restrict the spread of silencing: one of which involves a DNA binding element, whereas the other mechanism involves specific chromatin-modifying activities.

Chromatin↗

PubMed2004

Barrier proteins remodel and modify chromatin to restrict silenced domains.

Transcriptionally active and inactive domains are frequently found adjacent to one another in the eukaryotic nucleus. To better understand the underlying mechanisms by which domains maintain opposing transcription patterns, we performed a systematic genomewide screen for proteins that may block the spread of silencing in yeast. This analysis identified numerous proteins with efficient silencing blocking activities, and some of these have previously been shown to be involved in chromatin dynamics. We isolated subunits of Swi/Snf, mediator, and TFIID, as well as subunits of the Sas-I, SAGA, NuA3, NuA4, Spt10p, Rad6p, and Dot1p complexes, as barrier proteins. We demonstrate that histone acetylation and chromatin remodeling occurred at the barrier and correlated with a block to the spread of silencing. Our data suggest that multiple overlapping mechanisms were involved in delimiting silenced and active domains in vivo.

Acetylation↗

PubMed2002

Blockers and barriers to transcription: competing activities?

In the eukaryotic cell active and inactive genes reside adjacent to one another and are modulated by numerous regulatory elements. Insulator elements prevent the misregulation of adjacent genes by restricting the effects of the regulatory elements to specific domains. Enhancer blockers prevent enhancers from inadvertently activating neighboring genes, and recent results suggest that they might function by a conserved mechanism across species. These elements appear to disrupt enhancer-promoter "communications" by interacting with the regulatory elements and sequestering these elements into specific regions of the nucleus thus rendering them non-functional. Barrier elements insulate active genes from neighboring heterochromatin and recent results suggest that they function by specific localized recruitment of acetyltransferases that antagonize the spread of heterochromatin-associated deacetylases, thus preventing the propagation of heterochromatin.

Animals↗