Maybe you could increase the initating amount of cells and antibody used for ChIP. Based on my own experience, 1-2ng of ChIP-DNA can be gained from 5-10 million cells with 5-10 microgram of antibody. 

Hi Pavan

I have checked the cross link timings and the sample is getting sonicated at 50 cycles (30 secs on and 30 secs off ). The other issue is that I am using frozen tissue samples (biopsy material) and the tissue is very limiting. I am using Low cell ChIP kit from diagenode, followed by IPure Kit from the same.  I have already standardized my Ab via IHC and western and its coming fine as desired.

I need to ask 1 more thing, if any antibodies immunoexpression is low/ nil, will its ChIP work? 

Hi Xuelong Simon Wang

I have very less cells, as I am using frozen tissue samples.

Oh, in that way, you can refer a microChIP (μChIP) protocol, though I have never used before. And as Pavan said, a ChIP-grade (not IHC or WB) antibody is essential to get good IP results.

We have already standardize ChIP protocol for histone studies, so I guess its working. MicroChIP is a good option but will it support NGS? 

Moreover, I dont have any ChIP grade antibodies for my transcription factors.

couple of options: First, as suggested increase the number of cells and amount of antibody. But 10 ug of a polyclonal antibody should be enough for a transcription factor. Also, you can do multiple IPs and pool the IPed DNA before library prep. I hope after cross-linking your epitiope is not masked. Have you done a WB after cross-linking?