title: Bhlhb5 and Prdm8 form a repressor complex involved in neuronal circuit assembly.
abstract: Although transcription factors that repress gene expression play critical roles in nervous system development, their mechanism of action remains to be understood. Here, we report that the Olig-related transcription factor Bhlhb5 (also known as Bhlhe22) forms a repressor complex with the PR/SET domain protein, Prdm8. We find that Bhlhb5 binds to sequence-specific DNA elements and then recruits Prdm8, which mediates the repression of target genes. This interaction is critical for repressor function since mice lacking either Bhlhb5 or Prdm8 have strikingly similar cellular and behavioral phenotypes, including axonal mistargeting by neurons of the dorsal telencephalon and abnormal itch-like behavior. We provide evidence that Cadherin-11 functions as target of the Prdm8/Bhlhb5 repressor complex that must be repressed for proper neural circuit formation to occur. These findings suggest that Prdm8 is an obligate partner of Bhlhb5, forming a repressor complex that directs neural circuit assembly in part through the precise regulation of Cadherin-11.
authors.affiliation: Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Ross
authors.forename: Alejandra E
authors.initials: AE
authors.lastname: McCord
authors.forename: Cynthia
authors.initials: C
authors.lastname: Jung
authors.forename: Denize
authors.initials: D
authors.lastname: Atan
authors.forename: Stephanie I
authors.initials: SI
authors.lastname: Mok
authors.forename: Martin
authors.initials: M
authors.lastname: Hemberg
authors.forename: Tae-Kyung
authors.initials: TK
authors.lastname: Kim
authors.forename: John
authors.initials: J
authors.lastname: Salogiannis
authors.forename: Linda
authors.initials: L
authors.lastname: Hu
authors.forename: Sonia
authors.initials: S
authors.lastname: Cohen
authors.forename: Yingxi
authors.initials: Y
authors.lastname: Lin
authors.forename: Dana
authors.initials: D
authors.lastname: Harrar
authors.forename: Roderick R
authors.initials: RR
authors.lastname: McInnes
authors.forename: Michael E
authors.initials: ME
authors.lastname: Greenberg
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D004268:DNA-Binding Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011712:Pyramidal Tracts / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015820:Cadherins; D004268:DNA-Binding Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C488357:Bhlhe22 protein, mouse; C086960:osteoblast cadherin; C543643:PRDM8 protein, mouse