If your lysis buffer contains 1% SDS, it may be precipitating out of solution if the samples are at 4 degrees for too long.  Perhaps the SDS causes other material in the lysate to aggregate as well.  If it helps, this is what I do for ChIP experiments; Store the buffer at room temperature.  Lyse the cells and immediately sonicate (on ice, but I assume sonication provides enough heat to keep the SDS in solution).  Spin at 4 degrees for ten minutes, then immediately aliquot and dilute the lysate 1:10 (0.1% SDS is soluble).  When I use frozen lysates for ChIP, I thaw at room temperature and invert the tube to get the SDS back into solution.  Perhaps this will work for your lysates.  If not, you might be able to keep the precipitate from forming in the first place.  Good luck!

Thanks Michael for your tips. In fact I do have the 1% SDS buffer at RT and the precipitate is floating on the surface of the supernatant, don't think that is the SDS. I would say is lipid? And it seems to be a a phenomenon on HepG2 and other liver cells (also got the same in mouse primary hepatocytes, although smaller one). Others like HUVECs would not have it. Will see if we get someone that performed ChIP on HepG2 before if they encountered the same stuff. Thanks again!