Characterization of BHC80 in BRAF-HDAC complex, involved in neuron-specific gene repression.
BRAF-HDAC complex (BHC) has been shown to contain six components, including BHC80, and to mediate REST-dependent transcriptional repression of neuron-specific genes in non-neuronal cells. In this study, we have examined the functional role(s) of BHC80 in mouse tissues and human cultured cells. Two isoforms of mouse BHC80 were predominantly present in the central nervous system and spermatogenic cells. Human cultured cells also contained two isoforms of BHC80. Immunohistochemical analysis showed the presence of mouse BHC80 in the nucleus of neuronal cells in the hippocampus and cerebellum. The C-terminal region of human BHC80 containing PHD zinc-finger domain was capable of binding directly to each of five other components of BHC, and of organizing BHC mediating transcriptional repression. Moreover, two isoforms of human BHC80 were distinguished from each other by reduced binding to HDAC1 and HDAC2, despite the presence of the PHD finger domain. These results suggest that BHC80 presumably serves as a scaffold protein in BHC in neuronal as well as non-neuronal cells. A possible role of BHC80 in spermatogenesis is also suggested.
Graduate School of Life and Environmental Sciences and Institute of Applied Biochemistry, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan.
Shigeki
S
Iwase
Aya
A
Januma
Kiyoko
K
Miyamoto
Naomi
N
Shono
Arata
A
Honda
Junn
J
Yanagisawa
Tadashi
T
Baba
D017398:Alternative Splicing / Q000502:physiology; D000818:Animals; D001921:Brain / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D020033:Protein Isoforms; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology; D013737:Testis / Q000378:metabolism
C492635:Phf21a protein, mouse; D020033:Protein Isoforms; D019908:Proto-Oncogene Proteins c-raf; C492634:PHF21A protein, human; D006655:Histone Deacetylases