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The effect of CTCF binding sites destruction by CRISPR/Cas9 on transcription of metallothionein gene family in liver hepatocellular carcinoma.

Abstract：

:Chromatin spatial organization is essential for transcriptional modulation and stabilization. The pattern of DNA distal interplay form the multiple topological associating domains (TADs), and further assemble the functional compartmentalization with open and expression-active chromatin ("A" compartments) or closed and expression-inactive chromatin ("B" compartments) in genome, whose boundaries were defined by the high enrichment of CCCTC-binding factor (CTCF). Nevertheless, As a potential therapeutic strategy, changing the local chromatin architecture via adding or removing the CTCF binding sites in situ to regulate the transcription activity of genes within one TAD in cancer cells is poorly explored. In present study, we observed that the metallothionein (MT) family were all remarkably decreased in HCC of TCGA database, and MT genes family were located within a TAD of 1.2 Mb at 16q13 in order, and CTCF binding sites were distributed at the both sites of MT gene clusters. Furthermore, CRISPR/Cas9 was employed to destroy the CTCF binding sites at the vicinity of the MT family in human liver hepatocellular carcinoma (HCC) cell lines Huh-7 and HepG2. And the presence of up-regulated transcription of MTs were observed in Huh-7 and HepG2 cells compared to normal liver CRL-12461 cells. Moreover, the presence of the varying DNA interplay as well as H3K4me3 and H3K9me3 modification on different MT genes were observed after CTCF binding domain destruction compared to the control using chromosome conformation capture (3C) and chromatin immunoprecipitation (ChIP). Our results determined a potential way to regulate the transcription of a series of genes via changing the local genomic organization for diseases treatment.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Gong W,Liu Y,Qu H,Liu A,Sun P,Wang X

doi

10.1016/j.bbrc.2019.01.107

subject

Has Abstract

pub_date

2019-03-19 00:00:00

pages

530-538

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(19)30136-6

journal_volume

510

pub_type

杂志文章

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The effect of CTCF binding sites destruction by CRISPR/Cas9 on transcription of metallothionein gene family in liver hepatocellular carcinoma.