Ancestrally Duplicated Conserved Noncoding Element Suggests Dual Regulatory Roles of HOTAIR in cis and trans

Research output: Contribution to journalJournal articlepeer-review

Documents

HOTAIR was proposed to regulate either HoxD cluster genes in trans or HoxC cluster genes in cis, a mechanism that remains unclear. We have identified a 32-nucleotide conserved noncoding element (CNE) as HOTAIR ancient sequence that likely originated at the root of vertebrate. The second round of whole-genome duplication resulted in one copy of the CNE within HOTAIR and another copy embedded in noncoding transcript of HOXD11. Paralogous CNEs underwent compensatory mutations, exhibit sequence complementarity with respect to transcripts directionality, and have high affinity in vitro. The HOTAIR CNE resembled a poised enhancer in stem cells and an active enhancer in HOTAIR-expressing cells. HOTAIR expression is positively correlated with HOXC11 in cis and negatively correlated with HOXD11 in trans. We propose a dual modality of HOTAIR regulation where transcription of HOTAIR and its embedded enhancer regulates HOXC11 in cis and sequence complementarity between paralogous CNEs suggests HOXD11 regulation in trans.

Original languageEnglish
Article numberUNSP 101008
JournaliScience
Volume23
Issue number4
Pages (from-to)1-27
ISSN2589-0042
DOIs
Publication statusPublished - 2020

Bibliographical note

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Number of downloads are based on statistics from Google Scholar and www.ku.dk


No data available

ID: 239954304