Widespread lysine β-hydroxybutyrylation plays diverse regulatory roles and is reversibly regulated by p300 and HDAC1/2.

Lysine lactylation (Kla), an epigenetic mark triggered by lactate during glycolysis, including the Warburg effect, bridges metabolism and gene regulation. Enzymes such as p300 and HDAC1/3 have been pivotal in deciphering the regulatory dynamics of Kla, though questions about additional regulatory enzymes, their specific Kla substrates, and the underlying functional mechanisms persist. Here, we identify SIRT1 and SIRT3 as key "erasers" of Kla, shedding light on their selective regulation of both histone and non-histone proteins. Proteomic analysis in SIRT1/SIRT3 knockout HepG2 cells reveals distinct substrate specificities toward Kla, highlighting their unique roles in cellular signaling. Notably, we highlight the role of specific Kla modifications, such as those on the M2 splice isoform of pyruvate kinase (PKM2), in modulating metabolic pathways and cell proliferation, thereby expanding Kla’s recognized functions beyond epigenetics. Therefore, this study deepens our understanding of Kla’s functional mechanisms and broadens its biological significance.

Lysine succinylation is one of the major post-translational modifications occurring on histones and is believed to have significant roles in regulating chromatin structure and function. Currently, histone desuccinylation is widely believed to be catalyzed by members of the SIRT family deacetylases. Here, we report that histone desuccinylation is in fact primarily catalyzed by the class I HDAC1/2/3. Inhibition or depletion of HDAC1/2/3 resulted in a marked increase of global histone succinylation, whereas ectopic expression of HDAC1/2/3 but not their deacetylase inactive mutants downregulated global histone succinylation. We demonstrated that the class I HDAC1/2/3 complexes have robust histone desuccinylase activity in vitro. Genomic landscape analysis revealed that histone succinylation is highly enriched at gene promoters and inhibition of HDAC activity results in marked elevation of promoter histone succinylation. Furthermore, our integrated analysis revealed that promoter histone succinylation positively correlates with gene transcriptional activity. Collectively, we demonstrate that the class I HDAC1/2/3 but not the SIRT family proteins are the major histone desuccinylases particularly important for promoter histone desuccinylation. Our study thus sheds new light on the role of histone succinylation in transcriptional regulation.

Semi-transparent polymer solar cells (ST-PSCs) have attracted great attention recently because of their potential for application in smart windows, etc. Here, we fabricated ST-PSCs based on a low band-gap conjugated polymer, PTB7-Th, as the donor and a narrow band-gap n-type organic semiconductor (n-OS), ITVfIC, as the acceptor. The active layer (with a thickness of 100 nm) of the ST-PSC exhibits a high average transmittance (AT) of 73.46% in the wavelength range of 400–600 nm. The as-cast ST-PSC with 15 nm Ag as the cathode without any additive or thermal-annealing treatment shows a higher power conversion efficiency (PCE) of 8.21% with an AT of 33.7%, which is one of the highest values for ST-PSCs without extra treatment. In addition, the ST-PSCs show good thermal stability with 91% of their original PCE value retained after high temperature treatment at 200 °C for 2 hours. The higher PCE and good stability indicate that the ST-PSC has potential for practical application and the narrow bandgap ITVfIC could be a promising n-OS acceptor for the fabrication of ST-PSCs.