Functional Roles of Acetylated Histone Marks at Mouse Meiotic Recombination Hot Spots

ABSTRACT Meiotic recombination initiates following the formation of DNA double-strand breaks (DSBs) by the Spo11 endonuclease early in prophase I, at discrete regions in the genome coined “hot spots.” In mammals, meiotic DSB site selection is directed in part by sequence-specific binding of PRDM9, a polymorphic histone H3 (H3K4Me3) methyltransferase. However, other chromatin features needed for meiotic hot spot specification are largely unknown. Here we show that the recombinogenic cores of active hot spots in mice harbor several histone H3 and H4 acetylation and methylation marks that are typical of open, active chromatin. Further, deposition of these open chromatin-associated histone marks is dynamic and is manifest at spermatogonia and/or pre-leptotene-stage cells, which facilitates PRDM9 binding and access for Spo11 to direct the formation of DSBs, which are initiated at the leptotene stage. Importantly, manipulating histone acetylase and deacetylase activities established that histone acetylation marks are necessary for both hot spot activity and crossover resolution. We conclude that there are functional roles for histone acetylation marks at mammalian meiotic recombination hot spots.

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Multiple Modes of Chromatin Configuration at Natural Meiotic Recombination Hot Spots in Fission Yeast

Eukaryotic Cell ◽

10.1128/ec.00246-07 ◽

2007 ◽

Vol 6 (11) ◽

pp. 2072-2080 ◽

Cited By ~ 28

Author(s):

Kouji Hirota ◽

Walter W. Steiner ◽

Takehiko Shibata ◽

Kunihiro Ohta

Keyword(s):

Transcription Factor ◽

Fission Yeast ◽

Meiotic Recombination ◽

Hot Spots ◽

Hot Spot ◽

Micrococcal Nuclease ◽

Open Chromatin ◽

Sequence Motif ◽

Chromatin Configuration ◽

Recombination Hot Spots

ABSTRACT The ade6-M26 meiotic recombination hot spot of fission yeast is defined by a cyclic AMP-responsive element (CRE)-like heptanucleotide sequence, 5′-ATGACGT-3′, which acts as a binding site for the Atf1/Pcr1 heterodimeric transcription factor required for hot spot activation. We previously demonstrated that the local chromatin around the M26 sequence motif alters to exhibit higher sensitivity to micrococcal nuclease before the initiation of meiotic recombination. In this study, we have examined whether or not such alterations in chromatin occur at natural meiotic DNA double-strand break (DSB) sites in Schizosaccharomyces pombe. At one of the most prominent DSB sites, mbs1 (meiotic break site 1), the chromatin structure has a constitutively accessible configuration at or near the DSB sites. The establishment of the open chromatin state and DSB formation are independent of the CRE-binding transcription factor, Atf1. Analysis of the chromatin configuration at CRE-dependent DSB sites revealed both differences from and similarities to mbs1. For example, the tdh1 + locus, which harbors a CRE consensus sequence near the DSB site, shows a meiotically induced open chromatin configuration, similar to ade6-M26. In contrast, the cds1 + locus is similar to mbs1 in that it exhibits a constitutive open configuration. Importantly, Atf1 is required for the open chromatin formation in both tdh1 + and cds1 +. These results suggest that CRE-dependent meiotic chromatin changes are intrinsic processes related to DSB formation in fission yeast meiosis. In addition, the results suggest that the chromatin configuration in natural meiotic recombination hot spots can be classified into at least three distinct categories: (i) an Atf1-CRE-independent constitutively open chromatin configuration, (ii) an Atf1-CRE-dependent meiotically induced open chromatin configuration, and (iii) an Atf1-CRE-dependent constitutively open chromatin configuration.

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HELLS and PRDM9 form a pioneer complex to open chromatin at meiotic recombination hot spots

Genes & Development ◽

10.1101/gad.333542.119 ◽

2020 ◽

Vol 34 (5-6) ◽

pp. 398-412 ◽

Cited By ~ 8

Author(s):

Catrina Spruce ◽

Sibongakonke Dlamini ◽

Guruprasad Ananda ◽

Naomi Bronkema ◽

Hui Tian ◽

...

Keyword(s):

Meiotic Recombination ◽

Hot Spots ◽

Open Chromatin ◽

Recombination Hot Spots

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A Highly Polymorphic Meiotic Recombination Mouse Hot Spot Exhibits Incomplete Repair

Molecular and Cellular Biology ◽

10.1128/mcb.00874-07 ◽

2007 ◽

Vol 27 (20) ◽

pp. 7053-7062 ◽

Cited By ~ 22

Author(s):

Philippe R. J. Bois

Keyword(s):

Human Genome ◽

Meiotic Recombination ◽

Hot Spots ◽

Hot Spot ◽

Inbred Strains ◽

Heteroduplex Dna ◽

Mammalian Genomes ◽

Recombination Hot Spots ◽

Wild House Mouse ◽

Mature Spermatozoa

ABSTRACT The recent mapping of recombination hot spots in the human genome has demonstrated that crossover is a nonrandom process that occurs at well-defined positions along chromosomes. However, the mechanisms that direct hot-spot turnover in complex mammalian genomes are poorly understood. Analyses of the human genome are impaired by the inability to genetically dissect and molecularly manipulate recombinogenic regions to test their roles in regulating hot spots. Here, using the BXD recombinant inbred strains as a crossover library, three new recombination hot spots have been identified on mouse chromosome 19. Analyses of a highly polymorphic recombination hot spot (HS22) revealed that approximately 4% of recombinant molecules display complex and incomplete repair with discontinuous conversion tracts, as well as persistent heteroduplex DNA at crossover sites in mature spermatozoa. Also, sequence analysis of the wild house mouse revealed instability at the center of this hot spot. This suggests that complete repair is not required for completion of mammalian meiosis, a scenario that leaves duplex DNA containing mismatches at crossover sites.

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Natural Meiotic Recombination Hot Spots in the Schizosaccharomyces pombe Genome Successfully Predicted from the Simple Sequence Motif M26

Molecular and Cellular Biology ◽

10.1128/mcb.25.20.9054-9062.2005 ◽

2005 ◽

Vol 25 (20) ◽

pp. 9054-9062 ◽

Cited By ~ 38

Author(s):

Walter W. Steiner ◽

Gerald R. Smith

Keyword(s):

Schizosaccharomyces Pombe ◽

Meiotic Recombination ◽

Hot Spots ◽

Hot Spot ◽

Consensus Sequence ◽

Sequence Motif ◽

Dna Breaks ◽

Spot Activity ◽

In The Wild ◽

Recombination Hot Spots

ABSTRACT The M26 hot spot of meiotic recombination in Schizosaccharomyces pombe is the eukaryotic hot spot most thoroughly investigated at the nucleotide level. The minimum sequence required for M26 activity was previously determined to be 5′-ATGACGT-3′. Originally identified by a mutant allele, ade6-M26, the M26 heptamer sequence occurs in the wild-type S. pombe genome approximately 300 times, but it has been unclear whether any of these are active hot spots. Recently, we showed that the M26 heptamer forms part of a larger consensus sequence, which is significantly more active than the heptamer alone. We used this expanded sequence as a guide to identify a smaller number of sites most likely to be active hot spots. Ten of the 15 sites tested showed meiotic DNA breaks, a hallmark of recombination hot spots, within 1 kb of the M26 sequence. Among those 10 sites, one occurred within a gene, cds1 +, and hot spot activity of this site was confirmed genetically. These results are, to our knowledge, the first demonstration in any organism of a simple, defined nucleotide sequence accurately predicting the locations of natural meiotic recombination hot spots. M26 may be the first example among a diverse group of simple sequences that determine the distribution, and hence predictability, of meiotic recombination hot spots in eukaryotic genomes.

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Effects of Temperature on the Meiotic Recombination Landscape of the Yeast Saccharomyces cerevisiae

mBio ◽

10.1128/mbio.02099-17 ◽

2017 ◽

Vol 8 (6) ◽

Author(s):

Ke Zhang ◽

Xue-Chang Wu ◽

Dao-Qiong Zheng ◽

Thomas D. Petes

Keyword(s):

Saccharomyces Cerevisiae ◽

Gene Conversion ◽

Meiotic Recombination ◽

Hot Spots ◽

Genetic Maps ◽

Dna Breaks ◽

Low Levels ◽

C 30 ◽

Recombination Hot Spots ◽

In Cells

ABSTRACT Although meiosis in warm-blooded organisms takes place in a narrow temperature range, meiosis in many organisms occurs over a wide variety of temperatures. We analyzed the properties of meiosis in the yeast Saccharomyces cerevisiae in cells sporulated at 14°C, 30°C, or 37°C. Using comparative-genomic-hybridization microarrays, we examined the distribution of Spo11-generated meiosis-specific double-stranded DNA breaks throughout the genome. Although there were between 300 and 400 regions of the genome with high levels of recombination (hot spots) observed at each temperature, only about 20% of these hot spots were found to have occurred independently of the temperature. In S. cerevisiae , regions near the telomeres and centromeres tend to have low levels of meiotic recombination. This tendency was observed in cells sporulated at 14°C and 30°C, but not at 37°C. Thus, the temperature of sporulation in yeast affects some global property of chromosome structure relevant to meiotic recombination. Using single-nucleotide polymorphism (SNP)-specific whole-genome microarrays, we also examined crossovers and their associated gene conversion events as well as gene conversion events that were unassociated with crossovers in all four spores of tetrads obtained by sporulation of diploids at 14°C, 30°C, or 37°C. Although tetrads from cells sporulated at 30°C had slightly (20%) more crossovers than those derived from cells sporulated at the other two temperatures, spore viability was good at all three temperatures. Thus, despite temperature-induced variation in the genetic maps, yeast cells produce viable haploid products at a wide variety of sporulation temperatures. IMPORTANCE In the yeast Saccharomyces cerevisiae , recombination is usually studied in cells that undergo meiosis at 25°C or 30°C. In a genome-wide analysis, we showed that the locations of genomic regions with high and low levels of meiotic recombination (hot spots and cold spots, respectively) differed dramatically in cells sporulated at 14°C, 30°C, and 37°C. Thus, in yeast, and likely in other non-warm-blooded organisms, genetic maps are strongly affected by the environment.

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Genome-wide identification of meiotic recombination hot spots detected by SLAF in peanut (Arachis hypogaea L.)

Scientific Reports ◽

10.1038/s41598-020-70354-x ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Xiaohua Wang ◽

Ping Xu ◽

Yan Ren ◽

Liang Yin ◽

Shuangling Li ◽

...

Keyword(s):

Arachis Hypogaea ◽

Meiotic Recombination ◽

Hot Spots ◽

Genome Wide ◽

Arachis Hypogaea L ◽

Recombination Hot Spots

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Meiotic recombination hot spots and human DNA diversity

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2003.1372 ◽

2004 ◽

Vol 359 (1441) ◽

pp. 141-152 ◽

Cited By ~ 65

Author(s):

Alec J. Jeffreys ◽

J. Kim Holloway ◽

Liisa Kauppi ◽

Celia A. May ◽

Rita Neumann ◽

...

Keyword(s):

Human Genome ◽

Meiotic Recombination ◽

Hot Spots ◽

Haplotype Diversity ◽

Mendelian Inheritance ◽

Human Diversity ◽

Fundamental Information ◽

Recombination Hot Spots ◽

Sperm Typing ◽

Very High

Meiotic recombination plays a key role in the maintenance of sequence diversity in the human genome. However, little is known about the fine–scale distribution and processes of recombination in human chromosomes, or how these impact on patterns of human diversity. We have therefore developed sperm typing systems that allow human recombination to be analysed at very high resolution. The emerging picture is that human crossovers are far from randomly distributed but instead are targeted into very narrow hot spots that can profoundly influence patterns of haplotype diversity in the human genome. These hot spots provide fundamental information on processes of human crossover and gene conversion, as well as evidence that they can violate basic rules of Mendelian inheritance.

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