Increased binding of stroke-induced long non-coding RNAs to the transcriptional corepressors Sin3A and coREST.
LncRNAs (long non-coding RNAs) are thought to play a significant role in cellular homeostasis during development and disease by interacting with CMPs (chromatin-modifying proteins). We recently showed that following transient focal ischemia, the expression of many lncRNAs was altered significantly in rat brain. We currently analyzed whether focal ischemia also alters the association of lncRNAs with the CMPs Sin3A and coREST (corepressors of the RE-1 silencing transcription factor). RIP (RNA immunoprecipitation) combined with lncRNA microarray analysis showed that 177 of the 2497 lncRNAs expressed in rat cerebral cortex showed significantly increased binding to either Sin3A or coREST following ischemia compared with sham. Of these, 26 lncRNAs enriched with Sin3A and 11 lncRNAs enriched with coREST were also up-regulated in their expressions after ischemia. A majority of the lncRNAs enriched with these CMPs were intergenic in origin. Evaluation of the expression profiles of corresponding protein-coding genes showed that their expression levels correlate with those of the lncRNAs with which they shared a common locus. This is the first study to show that stroke-induced lncRNAs might associate with CMPs to modulate the post-ischemic epigenetic landscape.
*Department of Neurological Surgery, University of Wisconsin, Madison, WI, U.S.A.
Ashutosh
A
Dharap
Courtney
C
Pokrzywa
Raghu
R
Vemuganti
D000818:Animals; D056970:Co-Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D056264:Sin3 Histone Deacetylase and Corepressor Complex
D056970:Co-Repressor Proteins; C000588854:CoREST protein, rat; D009419:Nerve Tissue Proteins; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D056264:Sin3 Histone Deacetylase and Corepressor Complex