5-Azadeoxycytidine-induced chromatin remodeling of the inactive X-linked HPRT gene promoter occurs prior to transcription factor binding and gene reactivation.

The Journal of Biological Chemistry
M D LittT P Yang

Abstract

During the process of 5-aza-2'-deoxycytidine (5aCdr)-induced reactivation of the X-linked human hypoxanthine phosphoribosyltransferase (HPRT) gene on the inactive X chromosome, acquisition of a nuclease-sensitive chromatin conformation in the 5' region occurs before the appearance of HPRT mRNA. In vivo footprinting experiments reported here show that the 5aCdr-induced change in HPRT chromatin structure precedes the appearance of three footprints in the immediate 5' flanking region that are characteristic of the active HPRT allele. These and other data suggest the following sequence of events that lead to the reactivation of the HPRT gene after 5aCdr treatment: (a) hemi-demethylation of the promoter, (b) an "opening" of chromatin structure detectable as increased nuclease sensitivity, (c) transcription factor binding to the promoter, (d) assembly of the transcription complex, and (e) synthesis of HPRT RNA. This sequence of events supports the view that inactive X-linked genes are silenced by a repressive chromatin structure that prevents the binding of transcriptional activators to the promoter.

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Citations

Dec 10, 1999·The Journal of Experimental Medicine·A HmadchaE Pintado
Apr 16, 2013·Nucleic Acids Research·Yoko ItoAdele Murrell
May 3, 2005·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·François Vigneault, Régen Drouin
Dec 23, 2015·Reproductive Biology and Endocrinology : RB&E·Zoë L VincentAnna P Ponnampalam
Mar 5, 2003·Journal of Cellular Biochemistry·Stephanie M CohenDavid G Kaufman
Dec 12, 2002·The Journal of Biological Chemistry·Corey D BraastadEric A Hendrickson
Nov 30, 2000·American Journal of Physiology. Gastrointestinal and Liver Physiology·Z DongB M Evers
Oct 29, 2003·Journal of Andrology·Tamara L J KellyJacquetta M Trasler

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