ABSTRACT
Tbx3, a T-box transcription factor, regulates key steps in development of the heart and other organ systems. Here, we identify Sox4 as an interacting partner of Tbx3. Pull-down and nuclear retention assays verify this interaction and in situ hybridization reveals Tbx3 and Sox4 to co-localize extensively in the embryo including the atrioventricular and outflow tract cushion mesenchyme and a small area of interventricular myocardium. Tbx3, SOX4, and SOX2 ChIP data, identify a region in intron 1 of Gja1 bound by all tree proteins and subsequent ChIP experiments verify that this sequence is bound, in vivo, in the developing heart. In a luciferase reporter assay, this element displays a synergistic antagonistic response to co-transfection of Tbx3 and Sox4 and in vivo, in zebrafish, drives expression of a reporter in the heart, confirming its function as a cardiac enhancer. Mechanistically, we postulate that Sox4 is a mediator of Tbx3 transcriptional activity.
Subject(s)
Connexin 43/genetics , Gene Expression Regulation , SOXC Transcription Factors/metabolism , T-Box Domain Proteins/metabolism , Transcription, Genetic , Amino Acid Sequence , Animals , COS Cells , Chlorocebus aethiops , Humans , Male , Mice , Molecular Sequence Data , SOXC Transcription Factors/chemistry , ZebrafishABSTRACT
The term heterochromatin has been applied to both large-scale, microscopically visible chromocentres and small-scale, silent genes located outside chromocentres. This may cause confusion in the interpretation of epigenetic marks for both features. The model plant Arabidopsis thaliana provides an excellent system to investigate composition and function of chromatin states at different levels of organization. In this review we will discuss recent developments in molecular networks underlying gene silencing and the relationship with visible heterochromatin in Arabidopsis.
