NDLI: Uncoupling of X-linked gene silencing from XIST binding by DICER1 and chromatin modulation on human inactive X chromosome

Content Provider	Springer Nature Link
Author	Kota, Satya Keerthi Roy Chowdhury, Debabani Rao, Lakshmi K. Padmalatha, Venkata Singh, Lalji Bhadra, Utpal
Copyright Year	2014
Abstract	In mammals, X-inactivation process is achieved by the cis-spreading of long noncoding Xist RNA over one of the female X chromosomes. The Xist binding accumulates histones H3 methylation and H4 hypoacetylation required for X inactivation that leads to proper dosage compensation of the X-linked genes. Co-transcription of Tsix, an antisense copy of Xist, blocks the Xist coating on the Xi. In mice ES cells, an RNase III enzyme Dicer1 disrupts Xist binding and methylated H3K27me3 accumulation on the Xi. Later, multiple reports opposed these findings raising a question regarding the possible role of Dicer1 in murine X silencing. Here, we show that reduction of DICER1 in human female cells increases XIST transcripts without compromising the binding of the XIST and histone tail modifications on the Xi. Moreover, DICER1-depleted cells show differential upregulation of many human X-linked genes by binding different amounts of acetylated histone predominantly on their active promoter sites. Therefore, X-linked gene silencing, which is thought to be coupled with the accumulation of XIST and heterochromatin markers on Xi can be disrupted in DICER1 depleted human cells. These results suggest that DICER1 has no apparent effect on the recruitment of heterochromatic markers on the Xi but is required for inactivation of differentially regulated genes for the maintenance of proper dosage compensation in differentiated cells.
Starting Page	249
Ending Page	262
Page Count	14
File Format	PDF
ISSN	00095915
Journal	Chromosoma
Volume Number	124
Issue Number	2
e-ISSN	14320886
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2014-11-27
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	XIST X inactivation DICER1 Heterochromatin Histone modifications Cell Biology Developmental Biology Biochemistry Human Genetics Animal Genetics and Genomics Eukaryotic Microbiology
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

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