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The Evf2 enhancer long noncoding RNA regulates enhancer interactions across megabase distances
Author(s) -
Kohtz Jhumku,
Cajigas Ivelisse,
Chakraborty Abhijit,
Bastidas Monique,
Swyter Kelsey S.,
Kohtz Sara J.,
Ay Ferhat
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.525.19
Subject(s) - enhancer , dlx5 , biology , gene , genetics , transcription (linguistics) , long non coding rna , rna , genome , transcription factor , computational biology , homeobox , linguistics , philosophy
A major question in genome biology is how genes are selectively targeted and regulated over megabase (Mb) distances in the genome. In this work, we show that Evf2, a Dlx5/6 ultraconserved enhancer (Dlx5/6UCE) long non‐coding RNA, regulates a small group of 6 genes that are asymmetrically‐positioned across 27 Mb in relation to the Evf2 transcription start site. Evf2 RNA forms large intranuclear clouds that localize to both activated (Umad1, ~1.6 Mb distant) and repressed (Akr1b8, ~27 Mb distant) target genes in mouse developing brain. Measurements between Dlx5/6UCE‐Umad1 and Dlx5/6UCE‐Akr1b8 support that Evf2 controls distances between Dlx5/6UCE and transcriptional targets in subpopulations of neuronal progenitors. Chromosome conformation capture (4Cseq) using the Dlx5/6UCE as bait identifies Evf2 regulated and Evf2 independent Dlx5/6UCE interactions throughout chromosome 6 (~150 Mb). However, gene expression analysis suggests that transcriptional changes occur at only a subset of Evf2‐regulated Dlx5/6UCE interacting sites, supporting a developmental regulation of enhancer promoter contacts prior to gene regulation. These studies support that an autosomal, cloud‐forming enhancer lncRNA regulates genes through both antisense and chromosome topological mechanisms, and controls 3‐D architecture across multi‐megabase regions of a chromosome. Support or Funding Information This work is funded by NIMH R01MH094653 and R01MH111267 to J.D.K This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .