Bdf1 Bromodomains Are Essential for Meiosis and the Expression of Meiotic-Specific Genes

Abstract

Bromodomain and Extra-terminal motif (BET) proteins play a central role in transcription regulation and chromatin signalling pathways. They are present in unicellular eukaryotes and in this study, the role of the BET protein Bdf1 has been explored in Saccharomyces cerevisiae. Mutation of Bdf1 bromodomains revealed defects on both the formation of spores and the meiotic progression, blocking cells at the exit from prophase, before the first meiotic division. This phenotype is associated with a massive deregulation of the transcription of meiotic genes and Bdf1 bromodomains are required for appropriate expression of the key meiotic transcription factor NDT80 and almost all the Ndt80-inducible genes, including APC complex components. Bdf1 notably accumulates on the promoter of Ndt80 and its recruitment is dependent on Bdf1 bromodomains. In addition, the ectopic expression of NDT80 during meiosis partially bypasses this dependency. Finally, purification of Bdf1 partners identified two independent complexes with Bdf2 or the SWR complex, neither of which was required to complete sporulation. Taken together, our results unveil a new role for Bdf1 –working independently from its predominant protein partners Bdf2 and the SWR1 complex–as a regulator of meiosis-specific genes.

Dual function of Swc5 in SWR remodeling ATPase activation and histone H2A eviction

“…In yeast cells, the SWR complex is targeted to the proximity of its sites of action, e.g. the promoters, by the affinity of the histone code reader modules to acetylated histone tails ( 35 , 36 ). SWR then engages the +1 nucleosome in a process driven by the affinity of the basic region in Swc2 to the exposed DNA region at the NFR ( 32 ).…”

“…Several of these subunits are histone code readers. For example, Bdf1, which contains tandem bromodomains, binds preferentially to the tetra-acetylated histone H4 tail ( 35 ). The YEATS-domain containing Yaf9 binds to acetylated and crotonylated histone H3 ( 36 , 37 ).…”

Selective BET bromodomain inhibition as an antifungal therapeutic strategy

“…The fungal BET protein Bdf1 has been characterized as a global transcriptional regulator in Saccharomyces cerevisiae , where it regulates over 500 genes 22 . S. cerevisiae Bdf1 ( Sc Bdf1) associates with acetylated histones H3 and H4 (refs 22 , 23 , 24 ) and with the general transcription factor TFIID 25 , and is a subunit of the SWR1 chromatin remodelling complex 24 26 27 . Sc Bdf1 is also important for chromatin compaction during sporulation 28 and for the salt stress response 29 .…”

Systematic genetic and proteomic screens during gametogenesis identify H2BK34 methylation as an evolutionary conserved meiotic mark

“…They are dramatically deacetylated after the induction of sporulation before becoming re-acetylated during the final maturation stages of spores. In addition, previous reports suggest that the acetylation of the N-terminal tail of H4 is important for nuclear compaction in spores as mediator by the BET protein Bdf1 [ 33 , 72 ]. Here, the MS-based quantification analysis reveals a close interplay between H4 acetylation and methylation during yeast sporulation.…”

“…However, the molecular mechanisms that underlie the modification of these amino acid residues remains to be discovered. One potential explanation yet to be explored is whether H4R3me can affect the recruitment of H4 ac binders, notably the BET proteins to acetylated lysine residues [ 72 ].…”