Xin Sun

Chromatin Remodeling and Transcription Factors in Early Cardiac Development

Mouse heart development is a complicated process regulated by various signal molecules and transcription factors. Recent studies have shown chromatin remodeling factors also play a role in this process.

Baf60c is a subunit of SWI/SNF chromatin remodeling complexes. During the early embryo development, Baf60c shows tissue-specific expression pattern in heart and perinodal cells. RNAi knockdown of Baf60c in mouse embryo generates severe cardiac defects as well as left-right asymmetry defects. However, due to the early death and pleiotropic phenotypes of RNAi knockdown mouse embryo, how Baf60c regulates heart development with cardiac transcription factors is not yet clearly understood.

My research goal is to elucidate the role of Baf60c in mouse embryo heart development as well as left-right asymmetry development. To avoid the general defects of Baf60c knockdown, I will construct a tissue-specific Baf60c knockout mouse line. Deletion of Baf60c specifically in embryonic heart or in different compartments of heart will help to understand what developmental role Baf60c plays.

To isolate potential transcription factors or other chromatin remodeling factors associating with Baf60c in vivo, I will also generate epitope-tagged Baf60c knock-in mice. How Baf60c cooperates with candidate transcription factors and regulate gene expression will also be studied in cultured cell lines. This information will help in understanding the role of Baf60c in the signal pathways controlling mouse heart development, and may help in congenital heart disease diagnosis and mechanism studies.