Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Whole genome functional characterization of RE1 silencers using a modified massively parallel reporter assay Both upregulation and downregulation by cis-regulatory elements help establish precise gene expression. Our understanding of how elements repress transcriptional activity is far more limited than activating elements. To address this gap, we characterized RE1, a group of transcriptional silencers bound by REST, on a genome-wide scale using an modified massively parallel reporter assay (MPRAduo). MPRAduo empirically defined a minimal binding strength of REST required for silencing (REST m-value), above which multiple cofactors colocalize and act to directly silence transcription. We identified 1,500 human variants that alter RE1 silencing and found their effect sizes are predictable when they overlap with REST binding sites above the m-value. In addition, we demonstrate that non-canonical REST binding motifs exhibit silencer function only if they precisely align two half sites with specific spacer length. Our results show mechanistic insights into RE1 silencer which allows us to predict its activity and effect of variants on RE1, providing a paradigm for performing genome-wide functional characterization of transcription factors binding sites.
15
The categories of this paper are: developmental
19
The categories of this paper are: epidemiology
6
The categories of this paper are: plant
9
The categories of this paper are: synthetic
27
The categories of this paper are: pathology
12
The categories of this paper are: behavior
21
The categories of this paper are: toxicology
11
The categories of this paper are: cognition
26
The categories of this paper are: biochemistry
18
The categories of this paper are: systems
7
The categories of this paper are: ecology
28
The categories of this paper are: communication
20
The categories of this paper are: pharmacology
31
The categories of this paper are: paleontology
32
The categories of this paper are: zoology
3
The categories of this paper are: evolutionary