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UVM Department of Cellular, Molecular, and Biomedical Sciences
September 29, 2020 @ 11:30 am - 12:30 pm
Online from 11:30AM-12:30PM – Join the seminar
“Temporal regulation of T3-dependent transcriptional programming by TRb in thyroid cells”
Graduate student in Dr. Frances Carr’s lab (CMB)
University of Vermont
Transcriptional programming in response to thyroid hormone (T3) is a dynamic and cell-type specific process with layers of complexity that are not yet understood. To function as a transcription factor and facilitate a T3 response in thyroid cells, the thyroid hormone receptor (TRb) must bind to response elements, recruit necessary co-factors, and direct changes in chromatin accessibility to alter transcription of its target genes. We have taken an integrated genomics approach to reveal both short and long-term T3-dependent changes in TRb genomic occupancy by CUT&RUN, chromatin accessibility by ATAC-seq, and gene expression by RNA-seq. Proximity ligation assays followed by mass spectrometry have revealed a panel of novel TRb binding partners that play varying roles in transcriptional regulation. Our previous work defined BRG1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, as a key TRb co-regulator. Therefore, we have focused our efforts on understanding the participation of SWI/SNF chromatin remodelers in the establishment of the proper TRβ gene regulatory program on a genome-wide scale. This work will further define the roles of epigenetic changes in response T3 that constitute a normal hormone response. TRβ is widely recognized as a tumor suppressor and a positive prognostic indicator, however the mechanisms by which it regulates tumor growth remain unclear. Our current efforts to define the TRβ cistrome in normal thyroid cells has uncovered new mechanisms of tumor suppression.