Summary
Epidermal and hair follicle development from surface ectodermal progenitor cells require coordinated changes in gene expression. Histone deacetylases alter gene expression programs through modification of chromatin and transcription factors. We find that deletion of ectodermal Hdac1 and Hdac2 results in dramatic failure of hair follicle specification and epidermal proliferation and stratification, phenocopying loss of the key ectodermal transcription factor p63. While expression of p63 and its positively regulated basal cell targets is maintained in Hdac1/2 deficient ectoderm, targets of p63-mediated repression, including p21, 14-3-3σ and p16/INK4a, are ectopically expressed, and HDACs bind and are active at their promoter regions in normal undifferentiated keratinocytes. Mutant embryos display increased levels of acetylated p53, which opposes p63 functions, and p53 is required for HDAC inhibitor-mediated p21 expression in keratinocytes. Our data identify critical requirements for HDAC1/2 in epidermal development, and indicate that HDAC1/2 directly mediate repressive functions of p63, and suppress p53 activity.
Stiff person syndrome (SPS) is a rare autoimmune disorder, with incidence of 1-2 persons per million. 1 It is characterized by progressive muscle stiffness, rigidity, and spasms affecting the axial and limb muscles. 2,3 Heightened sensitivity to stimuli such as noise, touch, and emotional distress, which can then set off muscle spasms, has also been noted. The result is increased muscle activity that can often be confused for seizures or psychogenic non-epileptic seizures.Autoantibodies against glutamic acid decarboxylase (GAD) are considered fundamental to SPS pathogenesis, and several other autoimmune diseases are associated with elevated GAD antibody
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