ABSTRACT
In all eukaryotes, the initiation of DNA replication requires a stepwise assembly of factors onto the origins of DNA replication. This is pioneered by the Origin Recognition Complex, which recruits Cdc6. Together, they bring Cdt1, which shepherds MCM2-7 to form the OCCM complex. Sequentially, a second Cdt1-bound hexamer of MCM2-7 is recruited by ORC-Cdc6 to form an MCM double hexamer, which forms a part of the pre-RC. Although the mechanism of ORC binding to DNA varies across eukaryotes, how ORC is recruited to replication origins in human cells remains an area of intense investigation. This review discusses how the chromatin environment influences pre-RC assembly, function, and, eventually, origin activity.
ABSTRACT
CREB binding protein (CBP) is a multifunctional transcriptional co-activator that interacts with a variety of transcription factors and acts as a histone acetyltransferase. In Drosophila, CBP mediated acetylation of histone H3 lysine 27 (H3K27ac) is a known hallmark of gene activation regulated by trithorax group proteins (trxG). Recently, we have shown that a histone kinase Ballchen (BALL) substantially co-localizes with H3K27ac at trxG target loci and is required to maintain gene activation in Drosophila. Here, we report a previously unknown interaction between BALL and CBP, which positively regulates H3K27ac. Analysis of genome-wide binding profile of BALL and CBP reveals major overlap and their co-localization at actively transcribed genes. We show that BALL biochemically interacts with CBP and depletion of BALL results in drastic reduction in H3K27ac. Together, these results demonstrate a previously unknown synergy between BALL and CBP and reveals a potentially new pathway required to maintain gene activation during development.
ABSTRACT
OBJECTIVES: To assess the impact of isolated oligohydramnios on Perinatal outcomes. METHODS: A prospective Cohort Study was conducted at the department of Obstetrics and Gynaecology, The Aga Khan University Hospital, Karachi, Pakistan. Pregnant women with isolated oligohydramnios were recruited for the study after obtaining informed consent. The mode of delivery and perinatal outcome were compared with women having normal amniotic fluid. RESULTS: Between 1st May 2005 and 30th December 2005 a total of 421 women were included in this study. Of these 421 women, 71 were exposed and 350 were unexposed. When compared to the unexposed group women with oligohydramnios had significantly lower birth weight babies and were delivered at a significantly earlier gestational age. However there was no statistical difference in the APGAR scores at birth and NICU admissions between the two groups. The number of inductions and caesareans done for foetal reasons were significantly higher in the exposed group. CONCLUSION: Isolated oligohydramnios is not associated with adverse perinatal outcomes. However, it increases the risk for labour induction and Caesarean section.
