Aberrant levels of histone modifications lead to chromatin malfunctioning and consequently to various developmental defects and human diseases. Therefore, the proteins bearing the ability to modify histones have been extensively studied and the molecular mechanisms of their action are now fairly well understood. However, little attention has been paid to naturally occurring alternative isoforms of chromatin modifying proteins and to their biological roles. In this review, we focus on mammalian KDM2A and KDM2B, the only two lysine demethylases whose genes have been described to produce also an alternative isoform lacking the N-terminal demethylase domain. These short KDM2A/B-SF isoforms arise through alternative promoter usage and seem to play important roles in development and disease. We hypothesise about the biological significance of these alternative isoforms, which might represent a more common evolutionarily conserved regulatory mechanism.

• Klíčová slova
• KDM2A; KDM2B; lysine demethylase; epigenetics; chromatin; alternative isoform; alternative promoter,
• MeSH
• doména Jumonji s histondemethylasami nedostatek   genetika   metabolismus   MeSH
• izoenzymy nedostatek   genetika   metabolismus   MeSH
• lidé MeSH
• nádory enzymologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• doména Jumonji s histondemethylasami MeSH
• izoenzymy MeSH

Histone modifications have a profound impact on the chromatin structure and gene expression and their correct establishment and recognition is essential for correct cell functioning. Malfunction of histone modifying proteins is associated with developmental defects and diseases and detailed characterization of these proteins is therefore very important. The lysine specific demethylase KDM2A is a CpG island binding protein that has been studied predominantly for its ability to regulate CpG island-associated gene promoters by demethylating their H3K36me2. However, very little attention has been paid to the alternative KDM2A isoform that lacks the N-terminal demethylation domain, KDM2A-SF. Here we characterized KDM2A-SF more in detail and we found that, unlike the canonical full length KDM2A-LF isoform, KDM2A-SF forms distinct nuclear heterochromatic bodies in an HP1a dependent manner. Our chromatin immunoprecipitation experiments further showed that KDM2A binds to transcriptionally silent pericentromeric regions that exhibit high levels of H3K36me2. H3K36me2 is the substrate of the KDM2A demethylation activity and the high levels of this histone modification in the KDM2A-bound pericentromeric regions imply that these regions are occupied by the demethylation deficient KDM2A-SF isoform.

• Klíčová slova
• H3K36me2, HP1a, KDM2A, alternative isoforms, pericentromeric heterochromatin,
• MeSH
• centromera metabolismus   MeSH
• chromozomální proteiny, nehistonové metabolismus   MeSH
• demetylace * MeSH
• doména Jumonji s histondemethylasami chemie   metabolismus   MeSH
• F-box proteiny chemie   metabolismus   MeSH
• heterochromatin metabolismus   MeSH
• homolog proteinu s chromoboxem 5 MeSH
• izoenzymy chemie   metabolismus   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• proteinové domény MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chromozomální proteiny, nehistonové MeSH
• doména Jumonji s histondemethylasami MeSH
• F-box proteiny MeSH
• heterochromatin MeSH
• homolog proteinu s chromoboxem 5 MeSH
• izoenzymy MeSH
• KDM2A protein, human MeSH Prohlížeč

• Publikační typ
• úvodníky MeSH