Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/145323
Title: IN VIVO DELETION OF CTCF IN THE HEART ABOLISHES DNA LOOPS AND INDUCES GLOBAL ECTOPIC ENHANCER INTERACTIONS
Authors: DOMINIC PAUL LEE KOK SHENG
ORCID iD:   orcid.org/0000-0001-6880-453X
Keywords: Chromatin, CTCF, Hi-C, Cardiovascular, Enhancer, Epigenetics
Issue Date: 26-Jan-2018
Citation: DOMINIC PAUL LEE KOK SHENG (2018-01-26). IN VIVO DELETION OF CTCF IN THE HEART ABOLISHES DNA LOOPS AND INDUCES GLOBAL ECTOPIC ENHANCER INTERACTIONS. ScholarBank@NUS Repository.
Abstract: Three-dimensional DNA structures underpin accurate gene expression and organ function. Anchored by CTCF, chromatin is proposed to organize into topologically-associated domains (TADs), and into DNA loops at sub-TAD levels. However, the role of CTCF for chromatin loops and interactions remains unclear. In addition, how these loops regulate genes around them have not been investigated. Here, we performed a high resolution Hi-C analysis in primary isolated cardiomyocytes from conditional Ctcf-knockout mice in vivo, and observed the global abolition of CTCF-anchored loops. The genome-wide transcription dysregulation was associated to either the loss of intra-loop enhancer-promoter (E-P) connections, or the gain of E-P interactions across loops. Strikingly, CTCF depletion is accompanied by de novo interactions. Our study points to a mammalian genome that possesses a surprisingly strong propensity towards spontaneous E-P interactions upon CTCF loop loss, resulting in a diseased transcriptional state, and manifest as organ failure. CTCF is thus a central player for specifying chromatin loop formation and enabling accurate E-P connections.
URI: http://scholarbank.nus.edu.sg/handle/10635/145323
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