The neuronal transcription factor Myt1L interacts via a conserved motif with the PAH1 domain of Sin3 to recruit the Sin3L/Rpd3L histone deacetylase complex

Abstract

The Sin3L/Rpd3L histone deacetylase (HDAC) complex is one of six major HDAC complexes in the nucleus, and its recruitment by promoter‐bound transcription factors is an important step in many gene transcription regulatory pathways. Here, we investigate how the Myt1L zinc finger transcription factor, important for neuronal differentiation and the maintenance of neuronal identity, recruits this complex at the molecular level. We show that Myt1L, through a highly conserved segment shared with its paralogs, interacts directly and specifically with the Sin3 PAH1 domain, binding principally to the canonical hydrophobic cleft found in paired amphipathic helix domain (PAH) domains. Our findings are relevant not only for other members of the Myt family but also for enhancing our understanding of the rules of protein–protein interactions involving Sin3 PAH domains.

PWWP2B Fine‐Tunes Adipose Thermogenesis by Stabilizing HDACs in a NuRD Subcomplex

“…However, the fact that HDACs execute global regulation in a variety of cell types makes them difficult to be useful targets for obesity‐associated diseases due to severe side effects. [ 13 , 14 , 15 , 16 , 17 ] HDAC complex may be recruited to specific DNA loci through physically interacting with defined transcription factors or regulators in a cellular context. Transcriptional factor ZEB1 (zinc‐finger E‐box‐binding homeobox 1) is reported to interact with HDAC1 to modulate metastasis in non‐small cell lung cancer.…”

“…[ 21 ] Thus, an alternative strategy to alleviate side effects of HDAC inhibitors is to aim the tissue‐ or cell‐specific component in HDAC protein complexes. [ 17 , 22 , 23 ] In this regard, it will be helpful to unravel how HDACs are assembled into transcriptional machinery to fine‐tune thermogenic gene expression.…”