Ancestrally Duplicated Conserved Noncoding Element Suggests Dual Regulatory Roles of HOTAIR in cis and trans
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Ancestrally Duplicated Conserved Noncoding Element Suggests Dual Regulatory Roles of HOTAIR in cis and trans. / Nepal, Chirag; Taranta, Andrzej; Hadzhiev, Yavor; Pundhir, Sachin; Mydel, Piotr; Lenhard, Boris; Müller, Ferenc; Andersen, Jesper B.
In: iScience, Vol. 23, No. 4, UNSP 101008, 2020, p. 1-27.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Ancestrally Duplicated Conserved Noncoding Element Suggests Dual Regulatory Roles of HOTAIR in cis and trans
AU - Nepal, Chirag
AU - Taranta, Andrzej
AU - Hadzhiev, Yavor
AU - Pundhir, Sachin
AU - Mydel, Piotr
AU - Lenhard, Boris
AU - Müller, Ferenc
AU - Andersen, Jesper B
N1 - Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.1016/j.isci.2020.101008
DO - 10.1016/j.isci.2020.101008
M3 - Journal article
C2 - 32268280
VL - 23
SP - 1
EP - 27
JO - iScience
JF - iScience
SN - 2589-0042
IS - 4
M1 - UNSP 101008
ER -
ID: 239954304