Genome-wide analysis reveals novel molecular features of mouse recombination hotspots

ABSTRACT Meiotic recombination predominantly occurs at discrete genomic loci called recombination hotspots, but the features defining these areas are still largely unknown (reviewed in refs

1–5). To allow a comprehensive analysis of hotspot-associated DNA and chromatin characteristics, we developed a direct molecular approach for mapping meiotic DNA double-strand breaks that

initiate recombination. Here we present the genome-wide distribution of recombination initiation sites in the mouse genome. Hotspot centres are mapped with approximately 200-nucleotide

precision, which allows analysis of the fine structural details of the preferred recombination sites. We determine that hotspots share a centrally distributed consensus motif, possess a

nucleotide skew that changes polarity at the centres of hotspots and have an intrinsic preference to be occupied by a nucleosome. Furthermore, we find that the vast majority of recombination

initiation sites in mouse males are associated with testis-specific trimethylation of lysine 4 on histone H3 that is distinct from histone H3 lysine 4 trimethylation marks associated with

transcription. The recombination map presented here has been derived from a homogeneous mouse population with a defined genetic background and therefore lends itself to extensive future

experimental exploration. We note that the mapping technique developed here does not depend on the availability of genetic markers and hence can be easily adapted to other species with

complex genomes. Our findings uncover several fundamental features of mammalian recombination hotspots and underline the power of the new recombination map for future studies of genetic

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Open access 11 May 2022 INSIGHTS INTO VARIATION IN MEIOSIS FROM 31,228 HUMAN SPERM GENOMES Article 03 June 2020 INTERFERENCE LENGTH REVEALS REGULARITY OF CROSSOVER PLACEMENT ACROSS SPECIES

Article Open access 17 October 2024 ACCESSION CODES PRIMARY ACCESSIONS GENBANK/EMBL/DDBJ * HQ704390 * HQ704391 GENE EXPRESSION OMNIBUS * GSE24438 DATA DEPOSITS ChIP-Seq data have been

deposited in the Gene Expression Omnibus under accession number GSE24438. _Prdm9_ complementary DNA sequences have been deposited in GenBank under accession numbers HQ704390 and HQ704391.

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genome. _Nature_ 458, 362–366 (2009) Article  ADS  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank M. Lichten (NCI, NIH) and P. Hsieh (NIDDK, NIH) for comments and

discussion. We are grateful to S. Sharmeen for her help with high-throughput sequencing. This work was supported in part by Basil O’Connor Starter Scholar Research Award Grant No. 5-FY07-667

from the March of Dimes Foundation (G.V.P.); NIH grant 1R01GM084104-01A1 from NIGMS (G.V.P.); New Investigator Start-up Grants FS71HU, R071HU and CS71HU from USUHS (G.V.P.); and the NIDDK

(NIH) Intramural Research Program (R.D.C.-O.). AUTHOR INFORMATION Author notes * Fatima Smagulova and Ivan V. Gregoretti: These authors contributed equally to this work. AUTHORS AND

AFFILIATIONS * Uniformed Services University of the Health Sciences, Bethesda, 20814, Maryland, USA Fatima Smagulova & Galina V. Petukhova * National Institute of Diabetes, Digestive and

Kidney Diseases, NIH, Bethesda, 20892, Maryland, USA Ivan V. Gregoretti, Kevin Brick, Pavel Khil & R. Daniel Camerini-Otero Authors * Fatima Smagulova View author publications You can

also search for this author inPubMed Google Scholar * Ivan V. Gregoretti View author publications You can also search for this author inPubMed Google Scholar * Kevin Brick View author

publications You can also search for this author inPubMed Google Scholar * Pavel Khil View author publications You can also search for this author inPubMed Google Scholar * R. Daniel

Camerini-Otero View author publications You can also search for this author inPubMed Google Scholar * Galina V. Petukhova View author publications You can also search for this author

inPubMed Google Scholar CONTRIBUTIONS F.S. performed all experiments. I.V.G., K.B. and P.K. performed computational data analyses. All authors contributed to experimental design. G.V.P. and

R.D.C.-O. designed and supervised the study. G.V.P. wrote the manuscript. All authors discussed the results and commented on the manuscript. CORRESPONDING AUTHORS Correspondence to R. Daniel

Camerini-Otero or Galina V. Petukhova. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION The

file contains Supplementary Text, Supplementary Figures 1-16 with legends, Supplementary Table 1, Supplementary Methods and Materials and additional references. (PDF 2679 kb) SUPPLEMENTARY

DATA This data file contains listings of the DSB hotspots. (XLS 585 kb) POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 POWERPOINT SLIDE FOR FIG. 2 POWERPOINT SLIDE FOR FIG. 3 RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Smagulova, F., Gregoretti, I., Brick, K. _et al._ Genome-wide analysis reveals novel molecular features of mouse

recombination hotspots. _Nature_ 472, 375–378 (2011). https://doi.org/10.1038/nature09869 Download citation * Received: 05 October 2010 * Accepted: 24 January 2011 * Published: 03 April 2011

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