Double gene knockdown leads to X‐chromosome reactivation (939.7)

• DOI: 10.1096/fasebj.28.1_supplement.939.7
• Publication Date: 2021-06-16T09:41:54Z
• Authors: Stacy Thomas; Smitha Sripathy; Vid Leko; Eric Foss; Uyen Lao; Antonio Bedalov
• Keywords: XIST; MeCP2

Rett Syndrome is a X‐linked brain disorder caused by mutation in one copy of the MeCP2 gene. This gene only expressed some cells due to X‐chromosome silencing, phenomenon that occurs all with two X chromosomes. After four cell divisions, each embryo randomly inactivates (Xi) and other (Xa) provides genetic code for cell. choice propagated through subsequent divisions. The exact mechanism initiation maintenance silencing unknown, but factors are known. Xist RNA coats Xi, acting as signal initiate maintain X‐silencing. DNA methylation at CpG islands makes chromatin less available hypoacteylated histones alter packaging We hypothesize future treatment option will be use Small hairpin RNAs (shRNAs) knockdown genes fundamental reactivate Xi cause more produce functional. shRNAs can reduce expression imposing post‐transcriptional control on mRNAs, which they complementary base‐pair. A shRNA library screen using (Xa)MeCP2/(Xi)MeCP2‐Luciferase‐Hygromycin Resistance mouse tail fibroblasts generated 82 possible involved In order validate these screens, efficiency has been tested qPCR was used measure amount X‐reactivation. Reducing Acvr1 dnmt1 results combination knockdown, increases frequency reactivation. Grant Funding Source : research supported part Cancer Center Support (CCSG) CURE Supplement: NCI 5