MAINE-Seq/Mnase-Seq/Nucleo-Seq

MAINE-Seq/Mnase-Seq

Micrococcal nuclease (MNase) is derived from Staphylococcus aureus, and its first use to determine chromatin structure dates back to 1975, when the method was called, variously, staphylococcal nuclease or micrococcal nuclease digestion of nuclei or chromatin.^{1, 2} With the advent of NGS, MNase digestion³ became more popular and the term MNase-Seq was coined finally⁴. The terms MNase-assisted isolation of nucleosomes sequencing (MAINE-seq)^{5, 6} Nucleo-Seq⁷, and Nuc-seq⁸ are not commonly used. MNase, fused to the protein of interest, has been also been used for calcium-dependent cleavage to study specific genomic loci in vivo (ChEC-seq)⁹.

In MNase-Seq, gDNA is treated with MNase. Sequences bound by chromatin proteins are protected from MNase digestion. Next, the DNA from the DNA-protein complexes is extracted and used to prepare a sequencing library. Deep sequencing provides accurate representation of the location of regulatory DNA-binding proteins in the genome¹⁰.

Pros:

• Can map nucleosomes and other DNA-binding proteins¹¹
• Can footprint subnucleosomal particles protecting as little as ~25 bp¹²
• Identifies location of various regulatory proteins in the genome
• Covers a broad range of regulatory sites

Cons:

• MNase sites might not account for the entire genome
• AT-dependent sequence bias¹³
• Integration of MNase with ChIP data is necessary to identify and differentiate similar protein-binding sites

• MAINE-Seq: Cusick M. E., Herman T. M., DePamphilis M. L. and Wassarman P. M. (1981) Structure of chromatin at deoxyribonucleic acid replication forks: prenucleosomal deoxyribonucleic acid is rapidly excised from replicating simian virus 40 chromosomes by micrococcal nuclease. Biochemistry 20: 6648-6658
• MAINE-Seq: Ponts N., Harris E. Y., Prudhomme J., Wick I., Eckhardt-Ludka C., et al. (2010) Nucleosome landscape and control of transcription in the human malaria parasite. Genome Res 20: 228-238
• MNase-Seq: Schlesinger F., Smith A. D., Gingeras T. R., Hannon G. J. and Hodges E. (2013) De novo DNA demethylation and noncoding transcription define active intergenic regulatory elements. Genome Res 23: 1601-1614
• 1. Sollner-Webb B. and Felsenfeld G. A comparison of the digestion of nuclei and chromatin by staphylococcal nuclease. Biochemistry. 1975;14:2915-2920
• 2. Axel R. Cleavage of DNA in nuclei and chromatin with staphylococcal nuclease. Biochemistry. 1975;14:2921-2925
• 3. Schones D. E., Cui K., Cuddapah S., et al. Dynamic regulation of nucleosome positioning in the human genome. Cell. 2008;132:887-898
• 4. Kuan P. F., Huebert D., Gasch A. and Keles S. A non-homogeneous hidden-state model on first order differences for automatic detection of nucleosome positions. Stat Appl Genet Mol Biol. 2009;8:Article29
• 5. Cusick M. E., Herman T. M., DePamphilis M. L. and Wassarman P. M. Structure of chromatin at deoxyribonucleic acid replication forks: prenucleosomal deoxyribonucleic acid is rapidly excised from replicating simian virus 40 chromosomes by micrococcal nuclease. Biochemistry. 1981;20:6648-6658
• 6. Ponts N., Harris E. Y., Prudhomme J., et al. Nucleosome landscape and control of transcription in the human malaria parasite. Genome Res. 2010;20:228-238
• 7. Valouev A., Johnson S. M., Boyd S. D., Smith C. L., Fire A. Z. and Sidow A. Determinants of nucleosome organization in primary human cells. Nature. 2011;474:516-520
• 8. Chodavarapu R. K., Feng S., Bernatavichute Y. V., et al. Relationship between nucleosome positioning and DNA methylation. Nature. 2010;466:388-392
• 9. Zentner G. E., Kasinathan S., Xin B., Rohs R. and Henikoff S. ChEC-seq kinetics discriminates transcription factor binding sites by DNA sequence and shape in vivo. Nat Commun. 2015;6:8733
• 10. Schones D. E., Cui K., Cuddapah S., et al. Dynamic regulation of nucleosome positioning in the human genome. Cell. 2008;132:887-898
• 11. Zentner G. E. and Henikoff S. Surveying the epigenomic landscape, one base at a time. Genome Biol. 2012;13:250
• 12. Henikoff J. G., Belsky J. A., Krassovsky K., MacAlpine D. M. and Henikoff S. Epigenome characterization at single base-pair resolution. Proc Natl Acad Sci U S A. 2011;108:18318-18323
• 13. Kensche P. R., Hoeijmakers W. A., Toenhake C. G., et al. The nucleosome landscape of Plasmodium falciparum reveals chromatin architecture and dynamics of regulatory sequences. Nucleic Acids Res. 2016;44:2110-2124

1. Yan H., Tian S., Slager S. L., Sun Z. and Ordog T. Genome-Wide Epigenetic Studies in Human Disease: A Primer on -Omic Technologies. Am J Epidemiol. 2016;183:96-109

1. Lavender C. A., Cannady K. R., Hoffman J. A., et al. Downstream Antisense Transcription Predicts Genomic Features That Define the Specific Chromatin Environment at Mammalian Promoters. PLoS Genet. 2016;12:e1006224
2. Rube H. T., Lee W., Hejna M., et al. Sequence features accurately predict genome-wide MeCP2 binding in vivo. Nat Commun. 2016;7:11025
3. de Dieuleveult M., Yen K., Hmitou I., et al. Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells. Nature. 2016;530:113-116
4. Cole H. A., Cui F., Ocampo J., et al. Novel nucleosomal particles containing core histones and linker DNA but no histone H1. Nucleic Acids Res. 2016;44:573-581
5. Deniz O., Flores O., Aldea M., Soler-Lopez M. and Orozco M. Nucleosome architecture throughout the cell cycle. Sci Rep. 2016;6:19729
6. Devaiah B. N., Case-Borden C., Gegonne A., et al. BRD4 is a histone acetyltransferase that evicts nucleosomes from chromatin. Nat Struct Mol Biol. 2016;23:540-548
7. Johnson G. D., Jodar M., Pique-Regi R. and Krawetz S. A. Nuclease Footprints in Sperm Project Past and Future Chromatin Regulatory Events. Sci Rep. 2016;6:25864
8. Kensche P. R., Hoeijmakers W. A., Toenhake C. G., et al. The nucleosome landscape of Plasmodium falciparum reveals chromatin architecture and dynamics of regulatory sequences. Nucleic Acids Res. 2016;44:2110-2124
9. Lombrana R., Alvarez A., Fernandez-Justel J. M., et al. Transcriptionally Driven DNA Replication Program of the Human Parasite Leishmania major. Cell Rep. 2016;16:1774-1786
10. Maehara K. and Ohkawa Y. Exploration of nucleosome positioning patterns in transcription factor function. Sci Rep. 2016;6:19620
11. Matveeva E., Maiorano J., Zhang Q., et al. Involvement of PARP1 in the regulation of alternative splicing. Cell Discov. 2016;2:15046
12. Mieczkowski J., Cook A., Bowman S. K., et al. MNase titration reveals differences between nucleosome occupancy and chromatin accessibility. Nat Commun. 2016;7:11485
13. Ramakrishnan S., Pokhrel S., Palani S., et al. Counteracting H3K4 methylation modulators Set1 and Jhd2 co-regulate chromatin dynamics and gene transcription. Nat Commun. 2016;7:11949
14. Wang M., Wang P., Tu L., et al. Multi-omics maps of cotton fibre reveal epigenetic basis for staged single-cell differentiation. Nucleic Acids Res. 2016;44:4067-4079