ZMYND8
Developmental stage
Highly expressed in fetal brain, with decreasing expression in postnatal stages.
Domain
The bromo domain is required for interaction with histone H4K16ac.
Isoform 1
The bromo domain is required for localization to DNA damage sites.
Isoform 17
The MYND-type zinc finger domain is required for localization to DNA damage sites.
The PWWP domain is required for interaction with histone H3.1K36me2.
Function
Chromatin reader that recognizes dual histone modifications such as histone H3.1 dimethylated at 'Lys-36' and histone H4 acetylated at 'Lys-16' (H3.1K36me2-H4K16ac) and histone H3 methylated at 'Lys-4' and histone H4 acetylated at 'Lys-14' (H3K4me1-H3K14ac) (PubMed:26655721, PubMed:27477906, PubMed:31965980, PubMed:36064715). May act as a transcriptional corepressor for KDM5D by recognizing the dual histone signature H3K4me1-H3K14ac (PubMed:27477906). May also act as a transcriptional corepressor for KDM5C and EZH2 (PubMed:33323928). Recognizes acetylated histone H4 and recruits the NuRD chromatin remodeling complex to damaged chromatin for transcriptional repression and double-strand break repair by homologous recombination (PubMed:25593309, PubMed:27732854, PubMed:30134174). Also activates transcription elongation by RNA polymerase II through recruiting the P-TEFb complex to target promoters (PubMed:26655721, PubMed:30134174). Localizes to H3.1K36me2-H4K16ac marks at all-trans-retinoic acid (ATRA)-responsive genes and positively regulates their expression (PubMed:26655721). Promotes neuronal differentiation by associating with regulatory regions within the MAPT gene, to enhance transcription of a protein-coding MAPT isoform and suppress the non-coding MAPT213 isoform (PubMed:30134174, PubMed:35916866, PubMed:36064715). Suppresses breast cancer, and prostate cancer cell invasion and metastasis (PubMed:27477906, PubMed:31965980, PubMed:33323928).
Involvement in disease
Mutations in ZMYND8 may be the cause of syndromic intellectual disability with variable cardiovascular, ophthalmologic and minor skeletal anomalies.
Tissue Specificity
Expressed in neurons (at protein level) (PubMed:36064715). Absent in astrocytes (at protein level) (PubMed:36064715). Expressed in all tissues examined with highest expression in brain, lung, pancreas, and placenta (PubMed:11003709, PubMed:35916866). Expressed in cutaneous T-cell lymphomas (CTCL) (PubMed:11149944).
Cellular localization
- Nucleus
- Chromosome
- Cytoplasm
- Sequestered in the cytoplasm through the interaction with DBN1 (PubMed:28966017). Localizes to sites of DNA damage in a KAT5-dependent and DNA poly (ADP-ribose)-dependent manner (PubMed:25593309, PubMed:27732854). On chromatin, localizes to demethylated regions, active promoters, and transcription start sites (PubMed:27732854, PubMed:36064715).
Alternative names
KIAA1125, PRKCBP1, RACK7, ZMYND8, MYND-type zinc finger-containing chromatin reader ZMYND8, Cutaneous T-cell lymphoma-associated antigen se14-3, Protein kinase C-binding protein 1, Rack7, Transcription coregulator ZMYND8, Zinc finger MYND domain-containing protein 8, CTCL-associated antigen se14-3