High Sensitivity Profiling of Chromatin Structure by MNase-SSP

Citations of this article
Mendeley users who have this article in their library.


A complete view of eukaryotic gene regulation requires that we accurately delineate how transcription factors (TFs) and nucleosomes are arranged along linear DNA in a sensitive, unbiased manner. Here we introduce MNase-SSP, a single-stranded sequencing library preparation method for nuclease-digested chromatin that enables simultaneous mapping of TF and nucleosome positions. As a proof of concept, we apply MNase-SSP toward the genome-wide, high-resolution mapping of nucleosome and TF occupancy in murine embryonic stem cells (mESCs). Compared with existing MNase-seq protocols, MNase-SSP markedly enriches for short DNA fragments, enabling detection of binding by subnucleosomal particles and TFs, in addition to nucleosomes. From these same data, we identify multiple, sequence-dependent binding modes of the architectural TF Ctcf and extend this analysis to the TF Nrsf/Rest. Looking forward, we anticipate that single stranded protocol (SSP) adaptations of any protein-DNA interaction mapping technique (e.g., ChIP-exo and CUT&RUN) will enhance the information content of the resulting data. Ramani et al. describe MNase-SSP, a single-stranded DNA sequencing library preparation method for profiling chromatin structure. MNase-SSP libraries harbor diminished sequence bias and capture shorter DNA fragments compared to traditional MNase-seq libraries. Applying MNase-SSP to murine embryonic stem cells enables simultaneous analysis of nucleosomal, subnucleosomal, and transcription factor-DNA interactions genome-wide.




Ramani, V., Qiu, R., & Shendure, J. (2019). High Sensitivity Profiling of Chromatin Structure by MNase-SSP. Cell Reports, 26(9), 2465-2476.e4. https://doi.org/10.1016/j.celrep.2019.02.007

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free