A Novel EID-1 Family Member, EID-2, Associates with Histone Deacetylases and Inhibits Muscle Differentiation

Satoshi Miyake,Yuka Yanagisawa,Yasuhito Yuasa

doi:10.1074/jbc.m212212200

Abstract

An EID-1 (E1A-like inhibitor of differentiation-1) inhibits differentiation by blocking the histone acetyltransferase activity of p300. Here we report a novel inhibitor of differentiation exhibiting homology to EID-1, termed EID-2 (EID-1-like inhibitor of differentiation-2). EID-2 inhibited MyoD-dependent transcription and muscle differentiation. Unlike EID-1, EID-2 did not block p300 activity. Interestingly, EID-2 associated with class I histone deacetylases (HDACs). The N-terminal portion of EID-2 was required for the binding to HDACs. This region was also involved in the transcriptional repression and nuclear localization, suggesting the importance of the involvement of HDACs in the EID-2 function. These results indicate a new family of differentiation inhibitors, although there are several differences in the biochemical mechanisms between EID-2 and EID-1.

Highlights

The terminal differentiation program is regulated both positively and negatively
Identification and Cloning of EID-2—According to EST sequences from a data base, it is suggested that an EID-1-related gene exists (National Center for Biotechnology Information BLAST Searches, accession numbers AA203157 and AA447078)
The higher expression clones exhibited marked cell death upon a shift to differentiation medium (DM) (Fig. 4, B, i and C, l). These results indicated that EID-2 had a similar phenotype to EID-1, that is, inhibition of muscle differentiation, when it was ectopically expressed in myoblasts, even though EID-2 did not have the ability to inhibit p300-mediated transactivation (Fig. 2B)

Summary

Introduction

The terminal differentiation program is regulated both positively and negatively. Among various tissues, skeletal muscle is one of the most well studied in terms of differentiation regulation [1, 2]. EID-2 inhibited MyoD-dependent transcription and muscle differentiation. The N-terminal portion of EID-2 was required for the binding to HDACs. This region was involved in the transcriptional repression and nuclear localization, suggesting the importance of the involvement of HDACs in the EID-2 function.

Results

Conclusion