Many-author paper out in Nature Communications on noncoding genetic variation and TF regulation in skin: nature.com/articles/s41467-0… Comprises MPRA, multiple genetic screens and 298 CUT&RUN samples in primary cells to make a resource for the field.
Figure 2g, a protein network derived from GWAS of polygenic skin disease writ-large, likely contains novel therapuetic targets, and drives home the high magnitude of association between skin disease risk and the two processes of keratinization and differentiation.
Thank you to all the authors, including those who helped from the @jengreitz, @lecong, and @WJGreenleaf labs, and @DaveLReynolds who started the project.
We find that certain TF families are more implicated in dysregulation by noncoding variation. Overall, the catalog suggests opportunities for noncoding variation to affect disease risk through altered TF binding, such as rs4704864 near NIPAL4.
In addition to MPRA of disease-linked genetic variants, we also catalog interactions between homeostasis TFs and noncoding variants in primary cells through population sampling CUT&RUN of 13 individuals.
We find that bound genetic variants in promoters have reduced effects on TF binding ("promoter buffering") and this is correlated with increased TF binding density - suggesting a "peer pressure" model to resist catastrophic effects from promoter mutation.
The helicase DDX21 is regulated by glucose binding in epidermal differentiation to live a second, non-nucleolar life; exciting story in Cell from W. Miao! authors.elsevier.com/sd/arti…
Thank you to Maria Carmo-Fonseca for the excellent Commentary cell.com/cell/fulltext/S0092…
Douglas Porter retweeted
Modified forms of easyCLIP biorxiv.org/cgi/content/shor… #bioRxiv
Douglas Porter retweeted
From the Khavari lab, easyCLIP is a UV crosslinking IP sequencing method for absolute quantification analysis of RNA-protein interactions
go.nature.com/3vcLtoB
Recurrent cancer mutations in RNA-binding proteins studied as a class with a new approach to doing and thinking about CLIP-seq. rdcu.be/cgxky Mutations in A1CF, KHDRBS2, PCBP1, and DDX3X have effects.
Douglas Porter retweeted
SARS-CoV2 has affected us all over the past year and particularly health care workers. The emergence of variants globally is deeply concerning. Sharing our work on 2 variants B.1.351 and B.1.1.7 🧵 1/n biorxiv.org/content/10.1101/…
Douglas Porter retweeted
SARS-CoV-2 B.1.1.7 and B.1.351 Spike variants bind human ACE2 with increased affinity biorxiv.org/cgi/content/shor… #bioRxiv
Douglas Porter retweeted
The proximal proteome of 17 SARS-CoV-2 proteins links to disrupted antiviral signaling and host translation biorxiv.org/cgi/content/shor… #bioRxiv
Douglas Porter retweeted
Excited to share the latest of my thesis work!
We started out wanting to evaluate techniques that study RNA binding proteins (CLIP and TRIBE) and ended up learning a bit about nuclear organization along the way!
biorxiv.org/content/10.1101/…
Untemplated RNA polymerases as molecular recorders of RNA location: Records of RNA localization through covalent tagging biorxiv.org/content/10.1101/…
This is the CLIP paper I wish I could have had back when I started grad school. I think there is a lot of really useful results/demonstrations in there for someone starting CLIP-seq biorxiv.org/content/10.1101/…
Douglas Porter retweeted
Review of methods to study #RNA-#protein interactions. Presenting an overview of current methods and points to consider when choosing an RNA-centric or protein-centric approach
#RNP #ncRNA
nature.com/articles/s41592-0…
My paper: Target selection by natural and redesigned PUF proteins. A first look at designed RNA networks in vivo ncbi.nlm.nih.gov/pubmed/2666…
