TY - JOUR
T1 - Opposing roles for the lncRNA haunt and its genomic locus in regulating HOXA gene activation during embryonic stem cell differentiation
AU - Yin, Yafei
AU - Yan, Pixi
AU - Lu, Jinlong
AU - Song, Guang
AU - Zhu, Yangyang
AU - Li, Zhaohui
AU - Zhao, Yi
AU - Shen, Bin
AU - Huang, Xingxu
AU - Zhu, Heng
AU - Orkin, Stuart H.
AU - Shen, Xiaohua
N1 - Funding Information:
We thank L. Yu, Y. Chen, Y. Wang, F. Tang, T. Xie, J. Wang, Q. Xi, P. Das, Y. Huang, and X.S. laboratory members for critical reading of the manuscript and insightful discussions. Grant support was provided by the National Basic Research Program of China (2012CB966703), the National Natural Science Foundation of China (81171906, 31471219), and the Center of Life Sciences (CLS) at Tsinghua University.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/5/7
Y1 - 2015/5/7
N2 - Long noncoding RNAs (lncRNAs) have been implicated in controlling various aspects of embryonic stem cell (ESC) biology, although the functions of specific lncRNAs, and the molecular mechanisms through which they act, remain unclear. Here, we demonstrate discrete and opposing roles for the lncRNA transcript Haunt and its genomic locus in regulating the HOXA gene cluster during ESC differentiation. Reducing or enhancing Haunt expression, with minimal disruption of the Haunt locus, led to upregulation or downregulation of HOXA genes, respectively. In contrast, increasingly large genomic deletions within the Haunt locus attenuated HOXA activation. The Haunt DNA locus contains potential enhancers of HOXA activation, whereas Haunt RNA acts to prevent aberrant HOXA expression. This work reveals a multifaceted model of lncRNA-mediated transcriptional regulation of the HOXA cluster, with distinct roles for a lncRNA transcript and its genomic locus, while illustrating the power of rapid CRISPR/Cas9-based genome editing for assigning lncRNA functions.
AB - Long noncoding RNAs (lncRNAs) have been implicated in controlling various aspects of embryonic stem cell (ESC) biology, although the functions of specific lncRNAs, and the molecular mechanisms through which they act, remain unclear. Here, we demonstrate discrete and opposing roles for the lncRNA transcript Haunt and its genomic locus in regulating the HOXA gene cluster during ESC differentiation. Reducing or enhancing Haunt expression, with minimal disruption of the Haunt locus, led to upregulation or downregulation of HOXA genes, respectively. In contrast, increasingly large genomic deletions within the Haunt locus attenuated HOXA activation. The Haunt DNA locus contains potential enhancers of HOXA activation, whereas Haunt RNA acts to prevent aberrant HOXA expression. This work reveals a multifaceted model of lncRNA-mediated transcriptional regulation of the HOXA cluster, with distinct roles for a lncRNA transcript and its genomic locus, while illustrating the power of rapid CRISPR/Cas9-based genome editing for assigning lncRNA functions.
UR - http://www.scopus.com/inward/record.url?scp=84929272870&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84929272870&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2015.03.007
DO - 10.1016/j.stem.2015.03.007
M3 - Article
C2 - 25891907
AN - SCOPUS:84929272870
SN - 1934-5909
VL - 16
SP - 504
EP - 516
JO - Cell stem cell
JF - Cell stem cell
IS - 5
ER -