Targeting of myocyte enhancer binding factor 2 (MEF2) proteins to the nucleus depends on a C-terminal bipartite nuclear localization signal (NLS). By expression of green fluorescent protein (GFP)/MEF2 fusion proteins in transfected myoblasts, we show that MEF2C contains an additional 13 amino acids domain, located immediately upstream of the NLS, which contributes to its nuclear retention. We also show that the NLS present in MEF2 proteins is required for efficient nuclear localization of histone deacetylase 4 (HDAC4). In muscle cells, transfected HDAC4 is largely cytoplasmic or, to a lesser extent, pancellular. Co-transfection of either MEF2A or MEF2C causes HDAC4 to accumulate in the nucleus in association with MEF2. This effect strongly depends on MEF2 NLS; it also requires the specific interaction of HDAC4 with MEF2, since the isolated NLS is not sufficient for targeting HDAC4 to the nucleus and other nuclear proteins, such as NF-Y, cannot substitute MEF2. Therefore, we demonstrate that HDAC4, different from HDAC5, is mainly a cytoplasmic resident protein, requiring a trans-acting NLS for nuclear localization. The physiological implications of MEF2 carrying its own inhibitor to the nucleus are discussed.
The nuclear localization domain of the MEF2 family of transcription factors shows member-specific features and mediates the nuclear import of histone deacetylase 4
Serena Borghi, Susanna Molinari, Giorgia Razzini, Flavia Parise, Renata Battini, Stefano Ferrari; The nuclear localization domain of the MEF2 family of transcription factors shows member-specific features and mediates the nuclear import of histone deacetylase 4. J Cell Sci 15 December 2001; 114 (24): 4477–4483. doi: https://doi.org/10.1242/jcs.114.24.4477
Download citation file:
Sign in
Client Account
Sign in via your institution
Sign in via ShibbolethAdvertisement
Cited by
Interviews with Biologists @ 100 conference speakers

Explore our interviews with keynote speakers from the Biologists @ 100 conference, hosted to celebrate our publisher’s 100th anniversary, where we discuss climate change and biodiversity with Hans-Otto Pörtner and Jane Francis, health and disease with Charles Swanton and emerging technologies with Manu Prakash and Jennifer Lippincott-Schwartz.
Introducing our new Associate Editors

In this Editorial, JCS Editor-in-Chief Michael Way welcomes five new Associate Editors to the JCS team. These Associate Editors will expand our support for the wider cell biology community and handle articles in immune cell biology, proteostasis, imaging and image analysis, plant cell biology, and stem cell biology and modelling.
The spatial choreography of mRNA biosynthesis

In their Review, André Ventura-Gomes and Maria Carmo-Fonseca detail the latest research progress and technological advancements that are helping to unlock how nuclear organisation underpins control of gene transcription and pre-mRNA splicing.
JCS-FocalPlane Training Grants

Early-career researchers - working in an area covered by JCS - who would like to attend a microscopy training course, please apply. Deadline dates for 2025 applications: 6 June 2025 (decision by week commencing 28 July 2025) and 5 September 2025 (decision by week commencing 20 October 2025).
The emerging roles of the endoplasmic reticulum in mechanosensing and mechanotransduction

In their Review, Jonathan Townson and Cinzia Progida highlight recently emerging evidence for a role of the endoplasmic reticulum in enabling a cell to sense and respond to changes in the extracellular mechanical environment.