First Lab Publication! Review connecting cfDNA and chromatin biology

Another bright spot for the Ramachandran lab in 2020 is our first publication reviewing epigenomic methods that probe cell-free DNA in disease. Our angle, in line with the lab focus, is how chromatin structures captured in the blood can inform us about the biological state of a person.

Circulating cell-free DNA (cfDNA) provides an opportunity to develop blood tests for cancer. cfDNA harbors tissue-based information from which it originates and is of major interest for detecting cancer mutations. Surprisingly, cfDNA is generated in our bodies similar to the laboratory methods used to profile how DNA is packaged in our cells. Our review highlights connections between cfDNA features beyond the DNA sequence and the state and identities of cells that give rise to cfDNA. cfDNA provides the means to apply knowledge from the field of DNA packaging towards diagnosing and understanding cancer in humans.

Lab’s first preprint is out!!!

Check it out here:

Here is a tweetorial on the paper:

Excited to share the first preprint from our lab!!! We started by asking a simple question of how proteins bound enhancers and ended up with really cool results on transcription factor cooperativity. 1/

We used short (<50 bp) MNase-protected fragments to identify TF binding at high-resolution in enhancers in Drosophila cells and found on average 4 (!!!) TF binding events within ~500 bp enhancers 2/

We found a way to use V-plots to ask if two of the TFs bound at the same time in these enhancers – and found most of the time they do! 3/

We orthogonally confirmed TFs binding at the same time using dSMF data generated by @arnaud_kr in the same cells

We also confirmed co-binding of TFs by comparing Native ChiP and CUT&RUN at GAGA factor (TRL) binding sites 5/

Finally, we saw cooperativity of TF binding at enhancers to correlate with BOTH nucleosome occupancy and turnover, pointing to cooperative binding as a means to displace nucleosomes from enhancers 6/

I want to thank my co-authors and collaboratorsr @satyaiiitm @KamiAhmad3. And this work wouldn't have been complete without amazing previous work from @AlexanderStark8 on STARR-seq and @arnaud_kr on dSMF!

Originally tweeted by Srinivas Ramachandran (@4everBiochemist) on August 18, 2020.

Srinivas selected as a Pew-Stewart Scholar

Very grateful for our research on plasma cell free-DNA to be recognized by the Pew Charitable Trusts and the Alexander and Margaret Stewart Trust.