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General Comment |
PRDM9 binding organizes hotspot nucleosomes and limits Holliday junction migration
Christopher L. Baker1,
Michael Walker1,
Shimpei Kajita1,2,
Petko M. Petkov1 and
Kenneth Paigen1,3
+ Author Affiliations
Abstract
In mammals, genetic recombination during meiosis is limited to a set of 1- to 2-kb regions termed hotspots. Their locations are predominantly determined by the zinc finger protein PRDM9, which binds to DNA in hotspots and subsequently uses its SET domain to locally trimethylate histone H3 at lysine 4 (H3K4me3). This sets the stage for double-strand break (DSB) formation and reciprocal exchange of DNA between chromatids, forming Holliday junctions. Here we report genome-wide analyses of PRDM9-dependent histone modifications using two inbred mouse strains differing only in their PRDM9 zinc finger domain. We show that PRDM9 binding actively reorganizes nucleosomes into a symmetrical pattern, creating an extended nucleosome-depleted region. These regions are centered by a consensus PRDM9 binding motif, whose location and identity was confirmed in vitro. We also show that DSBs are centered over the PRDM9 binding motif within the nucleosome-depleted region. Combining these results with data from genetic crosses, we find that crossing-over is restricted to the region marked by H3K4me3. We suggest that PRDM9-modified nucleosomes create a permissible environment that first directs the location of DSBs and then defines the boundaries of Holliday junction branch migration.
NCBI Summary:
The protein encoded by this gene is a transcriptional regulator and oncoprotein that may be involved in hematopoiesis, apoptosis, development, and cell differentiation and proliferation. The encoded protein can interact with CTBP1, SMAD3, CREBBP, KAT2B, MAPK8, and MAPK9. This gene can undergo translocation with the AML1 gene, resulting in overexpression of this gene and the onset of leukemia. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]
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Comment |
The relationship between Evi-1 expression and mouse ovarian follicular development. Li Y et al. The ecotropic viral integration site-1 (Evi-1) is a transcription factor with two sets of zinc finger domains. It is an important regulator of the transforming growth factor beta superfamily. In the present study, we investigated the spatiotemporal expression patterns of Evi-1 using immunohistochemistry in ovaries from neonatal mice, gonadotropin-induced immature mice and mice in estrous cycle. Positive staining for Evi-1 was detected in the cytoplasm of oocytes. In postnatal mice, a high level of Evi-1 immunostaining was found from day 1 to 6, an intermediate level from day 10 to 16 and a low level on day 23. After gonadotropin treatment, Evi-1 was mainly expressed in small follicles and exhibited a very low level in large antral follicles. During the estrous cycle, the expression of Evi-1 was higher in diestrus and estrus than in proestrus and metestrus. Real-time PCR was performed to examine the relationship between Evi-1 mRNA and ovulation related genes (Ptgs2, Tnfaip6, Has2, Cd44, C1qbp). At 4h after hCG treatment, Evi-1 mRNA was down-regulated whereas ovulation related genes were up-regulated. Overall, the results indicate that Evi-1 is expressed in a stage-specific manner during ovarian follicular development and may be involved in early follicle development.
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