Chromatin Protein Complexes Involved in Gene Repression in Lamina-associated Domains

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2024 Sep 25

PMID 39322756

Authors

Stefano G Manzo

Abdelghani Mazouzi

Christ Leemans

Tom van Schaik

Nadia Neyazi

Marjon S van Ruiten

Benjamin D Rowland

Thijn R Brummelkamp

Bas van Steensel

Affiliations

Soon will be listed here.

Abstract

Lamina-associated domains (LADs) are large chromatin regions that are associated with the nuclear lamina (NL) and form a repressive environment for transcription. The molecular players that mediate gene repression in LADs are currently unknown. Here, we performed FACS-based whole-genome genetic screens in human cells using LAD-integrated fluorescent reporters to identify such regulators. Surprisingly, the screen identified very few NL proteins, but revealed roles for dozens of known chromatin regulators. Among these are the negative elongation factor (NELF) complex and interacting factors involved in RNA polymerase pausing, suggesting that regulation of transcription elongation is a mechanism to repress transcription in LADs. Furthermore, the chromatin remodeler complex BAF and the activation complex Mediator can work both as activators and repressors in LADs, depending on the local context and possibly by rewiring heterochromatin. Our data indicate that the fundamental regulators of transcription and chromatin remodeling, rather than interaction with NL proteins, play a major role in transcription regulation within LADs.

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