LSD1 Controls Timely MyoD Expression via MyoD Core Enhancer Transcription

Publication date: 21 February 2017
Source:Cell Reports, Volume 18, Issue 8
Author(s): Isabella Scionti, Shinichiro Hayashi, Sandrine Mouradian, Emmanuelle Girard, Joana Esteves de Lima, Véronique Morel, Thomas Simonet, Maud Wurmser, Pascal Maire, Katia Ancelin, Eric Metzger, Roland Schüle, Evelyne Goillot, Frederic Relaix, Laurent Schaeffer
MyoD is a master regulator of myogenesis. Chromatin modifications required to trigger MyoD expression are still poorly described. Here, we demonstrate that the histone demethylase LSD1/KDM1a is recruited on the MyoD core enhancer upon muscle differentiation. Depletion of Lsd1 in myoblasts precludes the removal of H3K9 methylation and the recruitment of RNA polymerase II on the core enhancer, thereby preventing transcription of the non-coding enhancer RNA required for MyoD expression (CEeRNA). Consistently, Lsd1 conditional inactivation in muscle progenitor cells during embryogenesis prevented transcription of the CEeRNA and delayed MyoD expression. Our results demonstrate that LSD1 is required for the timely expression of MyoD in limb buds and identify a new biological function for LSD1 by showing that it can activate RNA polymerase II-dependent transcription of enhancers.

Graphical abstract

Teaser

Scionti et al. show that LSD1 is recruited on the MyoD core enhancer, where it promotes the transcription of an enhancer RNA that controls the timing of MyoD expression during myoblast commitment. This provides the first evidence that LSD1 is required for the transcription of enhancer RNAs from a pro-differentiation enhancer.


http://ift.tt/2l7fphh