BRD4 expression in microglia supports recruitment of T cells into the CNS and exacerbates EAE.

Unlabelled: In EAE, a mouse model of multiple sclerosis, immunization with MOG autoantigen results in the generation of Th1/Th17 T cells in the periphery. MOG-specific T cells then invade into the central nervous system (CNS), resulting in neuronal demyelination. Microglia, innate immune cells in the CNS are known to regulate various neuronal diseases.

The nuclear transcription factor, TAF7, is a cytoplasmic regulator of protein synthesis.

The TFIID component, TAF7, has been extensively characterized as essential for transcription and is critical for cell proliferation and differentiation. Here, we report that TAF7 is a previously unknown RNA chaperone that contributes to the regulation of protein synthesis. Mechanistically, TAF7 binds RNAs in the nucleus and delivers them to cytoplasmic polysomes.

The Bromodomain Protein 4 Contributes to the Regulation of Alternative Splicing.

The bromodomain protein 4 (BRD4) is an atypical kinase and histone acetyl transferase (HAT) that binds to acetylated histones and contributes to chromatin remodeling and early transcriptional elongation. During transcription, BRD4 travels with the elongation complex. Since most alternative splicing events take place co-transcriptionally, we asked if BRD4 plays a role in regulating alternative splicing.

Immature CD8 Single-Positive Thymocytes Are a Molecularly Distinct Subpopulation, Selectively Dependent on BRD4 for Their Differentiation.

T cell differentiation in the thymus proceeds in an ordered sequence of developmental events characterized by variable expression of CD4 and CD8 coreceptors. Here, we report that immature single-positive (ISP) thymocytes are molecularly distinct from all other T cell populations in the thymus in their expression of a gene profile that is dependent on the transcription factor BRD4. Conditional deletion of BRD4 at various stages of thymic differentiation reveals that BRD4 selectively regulates the further differentiation of ISPs by targeting cell cycle and metabolic pathways, but it does not affect the extensive proliferation that results in the generation of ISPs.