Multivalency of nucleosome recognition by LEDGF

J 2023

Multivalency of nucleosome recognition by LEDGF

KOUTNA, Eliska, Vanda LUX, Tomas KOUBA, Jana SKERLOVA, Jiří NOVÁČEK et. al.

Basic information

Original name

Multivalency of nucleosome recognition by LEDGF

Authors

KOUTNA, Eliska, Vanda LUX, Tomas KOUBA, Jana SKERLOVA, Jiří NOVÁČEK (203 Czech Republic, belonging to the institution), Pavel SRB, Rozalie HEXNEROVA, Hana SVACHOVA, Zdenek KUKACKA, Petr NOVAK, Milan FABRY, Simon POEPSEL and Vaclav VEVERKA (guarantor)

Edition

Nucleic acids research, Oxford, Oxford University Press, 2023, 0305-1048

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 14.900 in 2022

RIV identification code

RIV/00216224:14740/23:00133766

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1093/nar/gkad674

UT WoS

001163598900001

Keywords in English

PWWP DOMAIN; RECOMBINANT HISTONES; STRUCTURAL BASIS; BINDING; REFINEMENT; ASSIGNMENT; DNA; COACTIVATOR

Abstract

V originále

Eukaryotic transcription is dependent on specific histone modifications. Their recognition by chromatin readers triggers complex processes relying on the coordinated association of transcription regulatory factors. Although various modification states of a particular histone residue often lead to differential outcomes, it is not entirely clear how they are discriminated. Moreover, the contribution of intrinsically disordered regions outside of the specialized reader domains to nucleosome binding remains unexplored. Here, we report the structures of a PWWP domain from transcriptional coactivator LEDGF in complex with the H3K36 di- and trimethylated nucleosome, indicating that both methylation marks are recognized by PWWP in a highly conserved manner. We identify a unique secondary interaction site for the PWWP domain at the interface between the acidic patch and nucleosomal DNA that might contribute to an H3K36-methylation independent role of LEDGF. We reveal DNA interacting motifs in the intrinsically disordered region of LEDGF that discriminate between the intra- or extranucleosomal DNA but remain dynamic in the context of dinucleosomes. The interplay between the LEDGF H3K36-methylation reader and protein binding module mediated by multivalent interactions of the intrinsically disordered linker with chromatin might help direct the elongation machinery to the vicinity of RNA polymerase II, thereby facilitating productive elongation.

Links

EF18_046/0015974, research and development project

Name: Modernizace České infrastruktury pro integrativní strukturní biologii

LM2023042, research and development project

Name: Česká infrastruktura pro integrativní strukturní biologii

Investor: Ministry of Education, Youth and Sports of the CR, CIISB - Czech Infrastructure for Integrative Structural Biology

90242, large research infrastructures

Name: CIISB III

Citovat

KOUTNA, Eliska, Vanda LUX, Tomas KOUBA, Jana SKERLOVA, Jiří NOVÁČEK, Pavel SRB, Rozalie HEXNEROVA, Hana SVACHOVA, Zdenek KUKACKA, Petr NOVAK, Milan FABRY, Simon POEPSEL and Vaclav VEVERKA. Multivalency of nucleosome recognition by LEDGF. Nucleic acids research. Oxford: Oxford University Press, 2023, vol. 51, No 18, p. 10011-10025. ISSN 0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkad674.

@article{2383603,
   author = {Koutna, Eliska and Lux, Vanda and Kouba, Tomas and Skerlova, Jana and Nováček, Jiří and Srb, Pavel and Hexnerova, Rozalie and Svachova, Hana and Kukacka, Zdenek and Novak, Petr and Fabry, Milan and Poepsel, Simon and Veverka, Vaclav},
   article_location = {Oxford},
   article_number = {18},
   doi = {http://dx.doi.org/10.1093/nar/gkad674},
   keywords = {PWWP DOMAIN; RECOMBINANT HISTONES; STRUCTURAL BASIS; BINDING; REFINEMENT; ASSIGNMENT; DNA; COACTIVATOR},
   language = {eng},
   issn = {0305-1048},
   journal = {Nucleic acids research},
   title = {Multivalency of nucleosome recognition by LEDGF},
   url = {https://academic.oup.com/nar/article/51/18/10011/7249925?login=true},
   volume = {51},
   year = {2023}
}

TY  - JOUR
ID  - 2383603
AU  - Koutna, Eliska - Lux, Vanda - Kouba, Tomas - Skerlova, Jana - Nováček, Jiří - Srb, Pavel - Hexnerova, Rozalie - Svachova, Hana - Kukacka, Zdenek - Novak, Petr - Fabry, Milan - Poepsel, Simon - Veverka, Vaclav
PY  - 2023
TI  - Multivalency of nucleosome recognition by LEDGF
JF  - Nucleic acids research
VL  - 51
IS  - 18
SP  - 10011-10025
EP  - 10011-10025
PB  - Oxford University Press
SN  - 03051048
KW  - PWWP DOMAIN
KW  - RECOMBINANT HISTONES
KW  - STRUCTURAL BASIS
KW  - BINDING
KW  - REFINEMENT
KW  - ASSIGNMENT
KW  - DNA
KW  - COACTIVATOR
UR  - https://academic.oup.com/nar/article/51/18/10011/7249925?login=true
N2  - Eukaryotic transcription is dependent on specific histone modifications. Their recognition by chromatin readers triggers complex processes relying on the coordinated association of transcription regulatory factors. Although various modification states of a particular histone residue often lead to differential outcomes, it is not entirely clear how they are discriminated. Moreover, the contribution of intrinsically disordered regions outside of the specialized reader domains to nucleosome binding remains unexplored. Here, we report the structures of a PWWP domain from transcriptional coactivator LEDGF in complex with the H3K36 di- and trimethylated nucleosome, indicating that both methylation marks are recognized by PWWP in a highly conserved manner. We identify a unique secondary interaction site for the PWWP domain at the interface between the acidic patch and nucleosomal DNA that might contribute to an H3K36-methylation independent role of LEDGF. We reveal DNA interacting motifs in the intrinsically disordered region of LEDGF that discriminate between the intra- or extranucleosomal DNA but remain dynamic in the context of dinucleosomes. The interplay between the LEDGF H3K36-methylation reader and protein binding module mediated by multivalent interactions of the intrinsically disordered linker with chromatin might help direct the elongation machinery to the vicinity of RNA polymerase II, thereby facilitating productive elongation.
ER  -

KOUTNA, Eliska, Vanda LUX, Tomas KOUBA, Jana SKERLOVA, Jiří NOVÁČEK, Pavel SRB, Rozalie HEXNEROVA, Hana SVACHOVA, Zdenek KUKACKA, Petr NOVAK, Milan FABRY, Simon POEPSEL and Vaclav VEVERKA. Multivalency of nucleosome recognition by LEDGF. \textit{Nucleic acids research}. Oxford: Oxford University Press, 2023, vol.~51, No~18, p.~10011-10025. ISSN~0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkad674.

Detailed Information on Publication Record