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@ARTICLE{PulidoCorts:302837,
author = {L. Pulido-Cortés$^*$ and H. Gielingh and V. Thijssen and
M. Liu and R. Yoshisada and L. Romão Soares and S.
Nizamuddin$^*$ and F. Friedrich and H. Greschik$^*$ and L.
Peng$^*$ and R. Vargas Honorato and M. Jung$^*$ and A. M. J.
J. Bonvin and M. L. Biniossek and R. Schüle$^*$ and S.
Jongkees and H. van Ingen and H. T. M. Timmers$^*$},
title = {{M}olecular determinants for recognition of serotonylated
chromatin.},
journal = {Nucleic acids research},
volume = {53},
number = {13},
issn = {0305-1048},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DKFZ-2025-01377},
pages = {gkaf612},
year = {2025},
abstract = {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.},
keywords = {Chromatin: metabolism / Chromatin: chemistry / Chromatin:
genetics / Histones: metabolism / Histones: chemistry /
Histones: genetics / Transcription Factor TFIID: chemistry /
Transcription Factor TFIID: metabolism / Transcription
Factor TFIID: genetics / TATA-Binding Protein Associated
Factors: chemistry / TATA-Binding Protein Associated
Factors: metabolism / TATA-Binding Protein Associated
Factors: genetics / Humans / Protein Binding / Protein
Processing, Post-Translational / Models, Molecular /
Epigenesis, Genetic / Binding Sites / RNA Polymerase II:
metabolism / RNA Polymerase II: genetics / Histone
Acetyltransferases / Chromatin (NLM Chemicals) / Histones
(NLM Chemicals) / Transcription Factor TFIID (NLM Chemicals)
/ TATA-Binding Protein Associated Factors (NLM Chemicals) /
TATA-binding protein associated factor 250 kDa (NLM
Chemicals) / RNA Polymerase II (NLM Chemicals) / Histone
Acetyltransferases (NLM Chemicals)},
cin = {FR01},
ddc = {570},
cid = {I:(DE-He78)FR01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40637225},
pmc = {pmc:PMC12238850},
doi = {10.1093/nar/gkaf612},
url = {https://inrepo02.dkfz.de/record/302837},
}