RT Journal Article
SR Electronic
T1 HERVH-derived lncRNAs negatively regulate chromatin targeting and remodeling mediated by CHD7
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101127
DO 10.26508/lsa.202101127
VO 5
IS 1
A1 Hsieh, Fu-Kai
A1 Ji, Fei
A1 Damle, Manashree
A1 Sadreyev, Ruslan I
A1 Kingston, Robert E
YR 2022
UL http://www.life-science-alliance.org/content/5/1/e202101127.abstract
AB Chd7 encodes an ATP-dependent chromatin remodeler which has been shown to target specific genomic loci and alter local transcription potentially by remodeling chromatin structure. De novo mutations in CHD7 are the major cause of CHARGE syndrome which features multiple developmental defects. We examined whether nuclear RNAs might contribute to its targeting and function and identified a preferential interaction between CHD7 and lncRNAs derived from HERVH loci in pluripotent stem cells. Knockdown of HERVH family lncRNAs using LNAs or knockout of an individual copy of HERVH by CRISPR-Cas9 both resulted in increased binding of CHD7 and increased levels of H3K27ac at a subset of enhancers. Depletion of HERVH family RNAs led to the activation of multiple genes. CHD7 bound HERVH RNA with high affinity but low specificity and this interaction decreased the ability of CHD7 to bind and remodel nucleosomes. We present a model in which HERVH lncRNAs act as a decoy to modulate the dynamics of CHD7 binding to enhancers in pluripotent cells and the activation of numerous genes that might impact the differentiation process.