HERVH-derived lncRNAs negatively regulate chromatin targeting and remodeling mediated by CHD7
Open Access
- 18 October 2021
- journal article
- research article
- Published by Life Science Alliance, LLC in Life Science Alliance
- Vol. 5 (1), e202101127
- https://doi.org/10.26508/lsa.202101127
Abstract
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.Funding Information
- National Institutes of Health (R01GM04390 and R35GM131743)
This publication has 72 references indexed in Scilit:
- Multiplexed Illumina sequencing libraries from picogram quantities of DNABMC Genomics, 2013
- An integrated encyclopedia of DNA elements in the human genomeNature, 2012
- The DNA-binding domain of the Chd1 chromatin-remodelling enzyme contains SANT and SLIDE domainsThe EMBO Journal, 2011
- Structure and function of SWI/SNF chromatin remodeling complexes and mechanistic implications for transcriptionProgress in Biophysics and Molecular Biology, 2010
- Transcriptome-wide Identification of RNA-Binding Protein and MicroRNA Target Sites by PAR-CLIPCell, 2010
- Molecular and phenotypic aspects of CHD7 mutation in CHARGE syndromeAmerican Journal of Medical Genetics Part A, 2010
- ATP Dependent Chromatin Remodeling Enzymes in Embryonic Stem CellsStem Cell Reviews and Reports, 2010
- CHD7 cooperates with PBAF to control multipotent neural crest formationNature, 2010
- Design and analysis of ChIP-seq experiments for DNA-binding proteinsNature Biotechnology, 2008
- New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioningJournal of Molecular Biology, 1998