title: Selective Recognition of H3.1K36 Dimethylation/H4K16 Acetylation Facilitates the Regulation of All-trans-retinoic Acid (ATRA)-responsive Genes by Putative Chromatin Reader ZMYND8.
abstract: ZMYND8 (zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8), a newly identified component of the transcriptional coregulator network, was found to interact with the Nucleosome Remodeling and Deacetylase (NuRD) complex. Previous reports have shown that ZMYND8 is instrumental in recruiting the NuRD complex to damaged chromatin for repressing transcription and promoting double strand break repair by homologous recombination. However, the mode of transcription regulation by ZMYND8 has remained elusive. Here, we report that through its specific key residues present in its conserved chromatin-binding modules, ZMYND8 interacts with the selective epigenetic marks H3.1K36Me2/H4K16Ac. Furthermore, ZMYND8 shows a clear preference for canonical histone H3.1 over variant H3.3. Interestingly, ZMYND8 was found to be recruited to several developmental genes, including the all-trans-retinoic acid (ATRA)-responsive ones, through its modified histone-binding ability. Being itself inducible by ATRA, this zinc finger transcription factor is involved in modulating other ATRA-inducible genes. We found that ZMYND8 interacts with transcription initiation-competent RNA polymerase II phosphorylated at Ser-5 in a DNA template-dependent manner and can alter the global gene transcription. Overall, our study identifies that ZMYND8 has CHD4-independent functions in regulating gene expression through its modified histone-binding ability.
authors.affiliation: From the Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata-700064 and the Structural Biology and Bioinformatics Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata-700032, India.
authors.forename: Santanu
authors.initials: S
authors.lastname: Adhikary
authors.affiliation: From the Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata-700064 and.
authors.forename: Sulagna
authors.initials: S
authors.lastname: Sanyal
authors.affiliation: From the Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata-700064 and.
authors.forename: Moitri
authors.initials: M
authors.lastname: Basu
authors.affiliation: From the Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata-700064 and.
authors.forename: Isha
authors.initials: I
authors.lastname: Sengupta
authors.affiliation: From the Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata-700064 and.
authors.forename: Sabyasachi
authors.initials: S
authors.lastname: Sen
authors.affiliation: the Structural Biology and Bioinformatics Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata-700032, India.
authors.forename: Dushyant Kumar
authors.initials: DK
authors.lastname: Srivastava
authors.affiliation: the Structural Biology and Bioinformatics Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata-700032, India roysiddhartha@iicb.res.in.
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Roy
authors.affiliation: From the Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata-700064 and chandrima.das@saha.ac.in.
authors.forename: Chandrima
authors.initials: C
authors.lastname: Das
mesh_terms: D000107:Acetylation / Q000187:drug effects; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D005786:Gene Expression Regulation / Q000187:drug effects*; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008745:Methylation / Q000187:drug effects; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics / Q000378:metabolism*; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins
chemical_list: D001324:Autoantigens; C115323:CHD4 protein, human; D002843:Chromatin; D006657:Histones; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C000617312:ZMYND8 protein, human; D014212:Tretinoin; D012319:RNA Polymerase II; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex
keywords: chromatin; chromatin modification; chromatin remodeling; gene expression; gene regulation; gene silencing; gene transcription