Histone H1 chaperone activity of TAF‐I is regulated by its subtype‐dependent intramolecular interaction

Abstract

Linker histone H1 is involved in the regulation of gene activity through the maintenance of higher-order chromatin structure. Previously, we have shown that template activating factor-I (TAF-I or protein SET) is involved in linker histone H1 dynamics as a histone H1 chaperone. In human and murine cells, two TAF-I subtypes exist, namely TAF-Iα and TAF-Iβ. TAF-I has a highly acidic amino acid cluster in its C-terminal region and forms homo- or heterodimers through its dimerization domain. Both dimer formation and the C-terminal region of TAF-I are essential for the histone chaperone activity. TAF-Iα exhibits less histone chaperone activity compared with TAF-Iβ even though TAF-Iα and β differ only in their N-terminal regions. However, it is unclear how subtype-specific TAF-I activities are regulated. Here, we have shown that the N-terminal region of TAF-Iα autoinhibits its histone chaperone activity via intramolecular interaction with its C-terminal region. When the interaction between the N- and C-terminal regions of TAF-Iα is disrupted, TAF-Iα shows a histone chaperone activity similar to that of TAF-Iβ. Taken together, these results provide mechanistic insights into the concept that fine tuning of TAF-I histone H1 chaperone activity relies on the subtype compositions of the TAF-I dimer.

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“…SET/TAF‐Iβ is a subtype of the SET/TAF‐I protein, belongs to the NAP family, and is also a well‐known human oncogene . The histone chaperone activity of SET/TAF‐Iβ depends on its extensive C‐terminal acidic region and requires the formation of homodimers or heterodimers with SET/TAF‐Iα subtype . SET/TAF‐Iβ dimers can bind to the linker and core histones to control chromatin dynamics .…”

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“…Histone modifiers, chromatin remodeling complexes, and histone chaperones are important factors in regulation of chromatin accessibility . Bioinformatics has revealed that the most transcriptionally active cis ‐elements, or transcriptionally poised genes are depleted of both nucleosome and histone H1 . Histone chaperones are responsible for nucleosome assembling/disassembling and histone variant exchange, and directly involved in gene transcription .…”

“…SET can evict linker histone H1 from the nucleosome, therefore overcoming H1-induced gene repression. 45,48 SET-α shows a lower histone H1 chaperone activity than SET-β due to isoelectric differences in its N-terminal region. Moreover, the N-terminal region of SET-α directly self-binds to the C-terminal region by intramolecular interaction, and therefore regulates the subtype composition-dependent histone H1 chaperone activity of the SET-α dimer.…”

“…Moreover, the N-terminal region of SET-α directly self-binds to the C-terminal region by intramolecular interaction, and therefore regulates the subtype composition-dependent histone H1 chaperone activity of the SET-α dimer. 45 Acetylation of histones by p300/CBP and PCAF is considered to be a critical step in transcriptional activation. Seo et al 49 The INHAT domain can bind to lysine residues at histone N-terminal tails and "masks" histones from histone acetyltransferases (HATs), therefore indirectly inhibiting HAT activity of p300/CBP.…”

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“…Although TAF-Iα differs from TAF-Iβ only in its N-terminal region, with the former having 37 amino acids (aa)and the latter having 24 aa, the histone chaperone activity of the TAF-Iα homo-dimer is significantly lower than that of the TAF-Iβ homodimer (Nagata et al 1995). Basic amino acids within the Nterminal region of TAF-Iα inhibit the histone chaperone activity via interaction with the C-terminal region (Kajitani et al 2017). It has been reported that the expression level of TAF-Iα varies among cell types compared with that of TAF-Iβ which is present ubiquitously at a relatively constant level (Nagata et al 1998), suggesting that the chaperone activity of TAF-I is regulated by the expression ratio of TAF-Iα and TAF-Iβ.…”