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HDAC1 negatively regulates selective mitotic chromatin binding of the Notch effector RBPJ in a KDM5A-dependent manner.
Nucleic Acids Res. 2019 05 21; 47(9):4521-4538.NA

Abstract

Faithful propagation of transcription programs through cell division underlies cell-identity maintenance. Transcriptional regulators selectively bound on mitotic chromatin are emerging critical elements for mitotic transcriptional memory; however, mechanisms governing their site-selective binding remain elusive. By studying how protein-protein interactions impact mitotic chromatin binding of RBPJ, the major downstream effector of the Notch signaling pathway, we found that histone modifying enzymes HDAC1 and KDM5A play critical, regulatory roles in this process. We found that HDAC1 knockdown or inactivation leads to increased RBPJ occupancy on mitotic chromatin in a site-specific manner, with a concomitant increase of KDM5A occupancy at these sites. Strikingly, the presence of KDM5A is essential for increased RBPJ occupancy. Our results uncover a regulatory mechanism in which HDAC1 negatively regulates RBPJ binding on mitotic chromatin in a KDM5A-dependent manner. We propose that relative chromatin affinity of a minimal regulatory complex, reflecting a specific transcription program, renders selective RBPJ binding on mitotic chromatin.

Authors+Show Affiliations

From the Department of Internal Medicine, Division of Molecular Medicine, Program in Cancer Genetics, Epigenetics and Genomics, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131, USA.From the Department of Internal Medicine, Division of Molecular Medicine, Program in Cancer Genetics, Epigenetics and Genomics, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131, USA.From the Department of Internal Medicine, Division of Molecular Medicine, Program in Cancer Genetics, Epigenetics and Genomics, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30916347

Citation

Dreval, Kostiantyn, et al. "HDAC1 Negatively Regulates Selective Mitotic Chromatin Binding of the Notch Effector RBPJ in a KDM5A-dependent Manner." Nucleic Acids Research, vol. 47, no. 9, 2019, pp. 4521-4538.
Dreval K, Lake RJ, Fan HY. HDAC1 negatively regulates selective mitotic chromatin binding of the Notch effector RBPJ in a KDM5A-dependent manner. Nucleic Acids Res. 2019;47(9):4521-4538.
Dreval, K., Lake, R. J., & Fan, H. Y. (2019). HDAC1 negatively regulates selective mitotic chromatin binding of the Notch effector RBPJ in a KDM5A-dependent manner. Nucleic Acids Research, 47(9), 4521-4538. https://doi.org/10.1093/nar/gkz178
Dreval K, Lake RJ, Fan HY. HDAC1 Negatively Regulates Selective Mitotic Chromatin Binding of the Notch Effector RBPJ in a KDM5A-dependent Manner. Nucleic Acids Res. 2019 05 21;47(9):4521-4538. PubMed PMID: 30916347.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HDAC1 negatively regulates selective mitotic chromatin binding of the Notch effector RBPJ in a KDM5A-dependent manner. AU - Dreval,Kostiantyn, AU - Lake,Robert J, AU - Fan,Hua-Ying, PY - 2019/03/07/accepted PY - 2019/02/28/revised PY - 2018/10/04/received PY - 2019/3/28/pubmed PY - 2019/11/22/medline PY - 2019/3/28/entrez SP - 4521 EP - 4538 JF - Nucleic acids research JO - Nucleic Acids Res. VL - 47 IS - 9 N2 - Faithful propagation of transcription programs through cell division underlies cell-identity maintenance. Transcriptional regulators selectively bound on mitotic chromatin are emerging critical elements for mitotic transcriptional memory; however, mechanisms governing their site-selective binding remain elusive. By studying how protein-protein interactions impact mitotic chromatin binding of RBPJ, the major downstream effector of the Notch signaling pathway, we found that histone modifying enzymes HDAC1 and KDM5A play critical, regulatory roles in this process. We found that HDAC1 knockdown or inactivation leads to increased RBPJ occupancy on mitotic chromatin in a site-specific manner, with a concomitant increase of KDM5A occupancy at these sites. Strikingly, the presence of KDM5A is essential for increased RBPJ occupancy. Our results uncover a regulatory mechanism in which HDAC1 negatively regulates RBPJ binding on mitotic chromatin in a KDM5A-dependent manner. We propose that relative chromatin affinity of a minimal regulatory complex, reflecting a specific transcription program, renders selective RBPJ binding on mitotic chromatin. SN - 1362-4962 UR - https://www.unboundmedicine.com/medline/citation/30916347/HDAC1_negatively_regulates_selective_mitotic_chromatin_binding_of_the_Notch_effector_RBPJ_in_a_KDM5A_dependent_manner_ L2 - https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkz178 DB - PRIME DP - Unbound Medicine ER -