Information for the 2019 Joint Research Center Seminar
Date	Wednesday, 2 October 2019, 17:00～18:30
Room	1st Floor, International Conference Room, Center for Smart-Aging Research, IDAC
Title	Macrophage production and functions in inflammatory diseases and regulated by TRIM33.
Speaker	Professor Paul-Henri Romeo (CEA, France)
Affiliation	The French Alternative Energies and Atomic Energy Commission (CEA)
Abstract	Macrophages are regulators of both tissue homeostasis and acquired diseases such as cancer, inflammatory diseases and bacterial and viral infections. The macrophage specific transcriptional programs are dictated by the transcription factor PU.1 that primes distal regulatory elements for macrophage identities and makes chromatin competent for activity of stimuli-dependent transcription factors. Although the functions of macrophage-specific distal regulatory elements that bind PU.1 have been elucidated, the underlying mechanisms of action of these cis-acting sequences are not characterized. The tripartite motif (TRIM) family of proteins plays important roles in innate immunity and antimicrobial infection but none of these proteins has been shown to directly regulate transcription of genes in macrophage. We will show that TRIM33 is recruited by PU.1 in a subset of macrophage specific regulatory sequences of genes involved in the inflammatory response and that sequestering of SPT16/FACT by TRIM33 at PU.1-bound distal regions might represent a new regulatory mechanism for RNA Pol II recruitment and transcription output in macrophages. Functionally, we will show that expression of TRIM33 in immature myeloid cells is necessary for efficient production of small peritoneal macrophages and bone marrow derived macrophage, that TRIM33 regulates macrophage function during inflammatory diseases such as Crohn’s disease and a previously unknown mechanism of macrophage-specific regulation of Ifnb1 transcription whereby TRIM33 is critical for Ifnb1 gene transcription shut down.