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.
Iwase
Shigeki
S
Graduate School of Life and Environmental Sciences and Institute of Applied Biochemistry, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8572, Japan.
Januma
Aya
A
Miyamoto
Kiyoko
K
Shono
Naomi
N
Honda
Arata
A
Yanagisawa
Junn
J
Baba
Tadashi
T
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