Thread by @LaurelCoons

DNA Sequence Constraints Define Functionally Active Steroid Nuclear Receptor Binding Sites in Chromatin:

1336 Datasets:

Defining NR Functional Enhancers (NRFEs)
#sNRFunctionalNRFE

Enhancer Activation
#IndicatorNRFE

sNR Cross-Talk
#sNRCrossTalkNRFE

doi.org/10.1210/en.201…

Functional Genomics:

📌Describes the relationship between an organism’s genotype (genetic makeup, DNA sequence) and phenotype (observable traits) on a global scale

📌A key characteristic is the genome-wide scale, rather than a more traditional “gene-by-gene” approach

#Genomics

DNA→RNA→Protein:

📌Genes:
-Blueprint for life
-Made of DNA
-Act as instructions to make proteins

📌Gene Expression:
DNA sequence is first copied to make an RNA molecule (transcription),
which is then "decoded" to build a protein (translation)

Proteins=Building Blocks Of Life

Transcription Is The First Step In Gene Expression

Transcription Initiation Complex:

📌Requires contact w/ activator proteins

📌Activator proteins bind to enhancers (far away)

📌A large # of activator proteins have been identified, including steroid nuclear receptors (sNRs)

Steroid Hormones Bind To & Activate sNRs:

✔️Estrogen→Estrogen Receptor

✔️Androgen→Androgen Receptor

✔️Progestin→Progesterone Receptor

✔️Glucocorticoid→Glucocorticoid Receptor

✔️Mineralocorticoid→Mineralocorticoid Receptor

#NuclearReceptor
#TranscriptionFactor

Identifying Where sNRs Interact With DNA:

📌ChIP-Seq: Used to identify where a protein interacts with the genomic DNA

📌>3000 published studies have used ChIP-Seq

📌The final readout is a list of peak locations in the genome (each peak is defined by a start point & end point)

ChIP-Seq:

📌Detects protein-DNA coassociation

📌The Problem
Most proteins show widespread association with genomic DNA

📌Distinguishing functional protein-DNA coassociation from nonfunctional is a challenge for every field in biology

Detected ChIP-Seq peaks on chromosomes👇

The DNA Sequence Defines Functionally Active sNR Binding Sites

📌Only small fraction of the protein-DNA interactions result in gene expression

📌This functionality is restricted to the consensus element and DNA elements that vary from the consensus element by 1 or 2 nucleotides