What are the disadvantages of native ChIP?

One disadvantage is that it is typically not applicable to non-histone proteins. Another disadvantage is that there may be selective digestion of specific chromatin domains during preparation. A third disadvantage is that there is a risk of protein rearrangement during chromatin preparation and precipitation. Native ChIP can also only shear chromatin enzymatically. Additionally, some low abundant transcription factors will not be detected while using native ChIP.