Molecular elements of the regulatory control of keratin filament modulator AHF/trichohyalin in the hair follicle

: Hairs in mammals undergo well‐programmed cyclic development, which is strictly controlled by the surrounding hair follicle cells. Among hair follicle epithelia the inner root sheath (IRS) directly envelops the hair shaft to mechanically support its cyclic growth, but the molecular mechanism underlying its sharp regulation remains obscure. Here, we identify regulatory elements for the expression of the IRS‐specific protein AHF (Anagenic Hair Follicle antigen), the putative mouse orthologue of trichohyalin (THH), which plays a key role in the assembly of keratin intermediate filaments (IFs) during the hair cycle. AHF becomes abundantly present in the growing anagenic hair follicle and is suddenly diminished as the tissue enters into the subsequent resting stages under the control of ubiquitin‐dependent proteolysis. Using primary human keratinocytes, we found that bone morphogenic protein‐4 facilitates THH transcription, and intriguingly, a nuclear lamina component plays a key role in the posttranslational stabilization of THH protein. Silencing of the lamin A/C gene leads to rapi THH degradation, whereas exogenously introduced lamin C, but not lamin A, protects THH from proteolytic elimination. These results shed light on the strict molecular mechanisms which control stage‐ and compartment‐specific IF assemblies in support of the cyclic development of the hair shaft.