CTCF Degradation Causes Increased Usage of Upstream Exons in Mouse Embryonic Stem Cells

TL;DR

This study investigates how degrading CTCF in mouse embryonic stem cells affects gene splicing, revealing increased usage of upstream exons likely due to transcriptional pausing caused by CTCF loss.

Contribution

It provides new insights into CTCF's role in gene regulation by linking its degradation to changes in alternative splicing patterns in stem cells.

Findings

Degradation of CTCF increases upstream exon usage.

CTCF depletion causes significant changes in gene expression.

Proposes transcriptional pausing as a mechanism for splicing regulation.

Abstract

Transcriptional repressor CTCF is an important regulator of chromatin 3D structure, facilitating the formation of topologically associating domains (TADs). However, its direct effects on gene regulation is less well understood. Here, we utilize previously published ChIP-seq and RNA-seq data to investigate the effects of CTCF on alternative splicing of genes with CTCF sites. We compared the amount of RNA-seq signals in exons upstream and downstream of binding sites following auxin-induced degradation of CTCF in mouse embryonic stem cells. We found that changes in gene expression following CTCF depletion were significant, with a general increase in the presence of upstream exons. We infer that a possible mechanism by which CTCF binding contributes to alternative splicing is by causing pauses in the transcription mechanism during which splicing elements are able to concurrently act on upstream exons already transcribed into RNA.