TY  - JOUR
AU  - Pulido-Cortés, Laura
AU  - Gielingh, Hajo
AU  - Thijssen, Vito
AU  - Liu, Minglong
AU  - Yoshisada, Ryoji
AU  - Romão Soares, Leonardo
AU  - Nizamuddin, Sheikh
AU  - Friedrich, Florian
AU  - Greschik, Holger
AU  - Peng, Ling
AU  - Vargas Honorato, Rodrigo
AU  - Jung, Manfred
AU  - Bonvin, Alexandre M J J
AU  - Biniossek, Martin L
AU  - Schüle, Roland
AU  - Jongkees, Seino
AU  - van Ingen, Hugo
AU  - Timmers, Hermanus Theodorus Marcus
TI  - Molecular determinants for recognition of serotonylated chromatin.
JO  - Nucleic acids research
VL  - 53
IS  - 13
SN  - 0305-1048
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DKFZ-2025-01377
SP  - gkaf612
PY  - 2025
AB  - Post-translational modifications of histone tails constitute a key epigenetic mechanism controlling chromatin environment and gene transcription. Serotonylation of histone H3Q5 (H3Q5ser) is a recently discovered mark associated with active transcription of RNA polymerase II (pol II)-transcribed genes. The direct link between H3Q5ser and the pol II transcription machinery relies on the TFIID subunit TAF3. The presence of H3Q5ser enhances TAF3 binding to H3K4me3, but the molecular determinants underlying this interaction remained unclear. Here, we resolve the binding mode of TAF3-PHD to H3K4me3Q5ser identifying a novel binding surface for H3Q5ser using solution nuclear magnetic resonance spectroscopy. This reveals how H3Q5ser recognizes a conserved surface of the TAF3-PHD via CH-π interactions in an edge-face conformation involving a proline residue stabilized by a tryptophan. This combination of proline and tryptophan is unique to the PHD finger of TAF3 and conserved among TAF3 orthologues. Our findings establish a framework for the molecular recognition of serotonylated chromatin, laying the foundation for developing epigenetic inhibitors targeting serotonylation-dependent transcriptional regulation in neuronal development.
KW  - Chromatin: metabolism
KW  - Chromatin: chemistry
KW  - Chromatin: genetics
KW  - Histones: metabolism
KW  - Histones: chemistry
KW  - Histones: genetics
KW  - Transcription Factor TFIID: chemistry
KW  - Transcription Factor TFIID: metabolism
KW  - Transcription Factor TFIID: genetics
KW  - TATA-Binding Protein Associated Factors: chemistry
KW  - TATA-Binding Protein Associated Factors: metabolism
KW  - TATA-Binding Protein Associated Factors: genetics
KW  - Humans
KW  - Protein Binding
KW  - Protein Processing, Post-Translational
KW  - Models, Molecular
KW  - Epigenesis, Genetic
KW  - Binding Sites
KW  - RNA Polymerase II: metabolism
KW  - RNA Polymerase II: genetics
KW  - Histone Acetyltransferases
KW  - Chromatin (NLM Chemicals)
KW  - Histones (NLM Chemicals)
KW  - Transcription Factor TFIID (NLM Chemicals)
KW  - TATA-Binding Protein Associated Factors (NLM Chemicals)
KW  - TATA-binding protein associated factor 250 kDa (NLM Chemicals)
KW  - RNA Polymerase II (NLM Chemicals)
KW  - Histone Acetyltransferases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40637225
C2  - pmc:PMC12238850
DO  - DOI:10.1093/nar/gkaf612
UR  - https://inrepo02.dkfz.de/record/302837
ER  -