Fig 1: The core module and tethering of its peripheral modules in human and yeast.a-c. Tethering of the HAT module: a. The N-terminus of SUPT7L runs parallel to the TAF6L linker, which connects to the HEAT domain, along the surface of the core and ends with its N-terminus in close proximity to the HEAT domain. b. In Saccharomyces cerevisiae4 (PDB: 6T9I), the Spt7 linker further extends towards the convex surface of the TAF6L HEAT domain and interacts with an unassigned region. c. The same region in Komagataella phaffii5 was assigned as the Ada3 subunit of the HAT module (PDB: 6TBM). The similar location of the SUPT7L N-terminus suggests a similar interaction and connectivity for the HAT module in hSAGA. d-f. Tethering the DUB module. d. The ATXN7 subunit of the core and the DUB module (Sgf73 in yeast) is similarly integrated into the core module as in ySAGA (e, f), suggesting a similar relative attachment of the human DUB. g. GraFix54 crosslinked negative stain class averages revealed extra density at the anticipated locations for the HAT (cyan arrow) and DUB (purple arrow) modules. h. The core of hSAGA and ySAGA (PDB: 6T9K) builds on common HF elements. Only HF containing subunits are shown. Architectural differences are created by local variations outside of the HFs. HF dimerization is indicated by arrows below the subunit labels. i. Comparison of TAF5 and TAF6 architecture within lobe A of human TFIID (canonical state9, PDB: 6MZL). TFIID contains two copies of TAF5 and TAF6, with one TAF5 located in lobe A (TAF5A) and the other one in lobe B (TAF5B), and with the two TAF6 HEAT domains (TAF6A, TAF6B) in lobe C (shown on the right). Compared to hSAGA, the TFIID TAF6 HEAT domains are differently arranged relative to TAF5, and they act to bridge lobes B and C. The TFIID TAF5 NTD is rotated by 90°, leading to a divergent architecture.