25 mg of frozen liver tissue was lysed to isolate ~25 μg genomic DNA using DNeasy blood & tissue kits (Qiagen). Adaptor oligonucleotides were synthesized by IDT (Supplementary Table 3 ). Transposon assembly was done by incubating 158ug Tn5 with 1.4 nmol annealed oligo (contains the full-length Illumina forward (i5) adapter, a sample barcode, and UMI)40 (link) at room temperature for 60 min.
For tagmentation, 200 ng of genomic DNA was incubated with 2 μl of assembled transposome at 55° for 7 min, and the product was cleaned up (20 μl) with a Zymo column (Zymo Research, #D4013). Tagmented DNA was used for the 1st PCR using PlatinumTM SuperFi DNA polymerase (Thermo) with i5 primer and gene-specific primers (Supplementary Table3 ). Four different libraries were prepared for gDNA from each mouse with different combinations of primers (i5+Locus_F [UDiTaS], i5+Locus_R [UDiTaS], i5+Insert_F [GUIDE-tag] and i5+Insert_R [GUIDE-tag]). The i7 index was added in the 2nd PCR and the PCR product was cleaned up with Ampure XP SPRI beads (Agencourt, 0.9X reaction volume). Completed libraries were quantified by Tapestation and Qubit (Agilent), pooled with equal mole, and sequenced with 150 bp paired-end reads on an Illumina MiniSeq instrument.
For tagmentation, 200 ng of genomic DNA was incubated with 2 μl of assembled transposome at 55° for 7 min, and the product was cleaned up (20 μl) with a Zymo column (Zymo Research, #D4013). Tagmented DNA was used for the 1st PCR using PlatinumTM SuperFi DNA polymerase (Thermo) with i5 primer and gene-specific primers (Supplementary Table
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