ZNHIT1

Description

The ZNHIT1 (zinc finger HIT-type containing 1) is a protein-coding gene located on chromosome 7.

ZNHIT1 plays a key role in chromatin remodeling by facilitating the incorporation of histone variant H2AZ1/H2A.Z into the genome, thereby regulating gene expression. It promotes the SRCAP complex-mediated deposition of H2AZ1 to lymphoid fate regulator genes, enhancing lymphoid lineage commitment. ZNHIT1 is recruited to the promoter of the transcriptional activator MYOG during early stages of muscle differentiation, mediating the binding of H2AZ1 to chromatin and inducing muscle-specific gene expression. Furthermore, ZNHIT1 maintains hematopoietic stem cell (HSC) quiescence by influencing chromatin accessibility at distal enhancers of HSC quiescence genes such as PTEN, FSTL1, and KLF4, promoting H2AZ1 deposition to sustain their transcription and restrict PI3K-AKT signaling inhibition. It also plays a vital role in intestinal stem cell maintenance by promoting H2AZ1 deposition at the transcription start sites of genes associated with intestinal stem cell fate determination, including LGR5, TGFB1, and TGFBR2, thereby contributing to gene transcription. ZNHIT1 promotes phosphorylation of the H2AZ1 chaperone VPS72/YL1, which enhances the interaction between H2AZ1 and VPS72. It regulates the entry of male germ cells into meiosis by controlling histone H2AZ1 deposition, facilitating the expression of meiotic genes such as MEIOSIN, leading to the initiation of meiosis. ZNHIT1 is essential for postnatal heart function, maintaining cardiac Ca(2+) homeostasis by modulating the expression of Ca(2+)-regulating proteins CASQ1 and ATP2A2/SERCA2A via H2AZ1 deposition at their promoters. During embryonic heart development, ZNHIT1 is crucial for mitochondrial maturation and oxidative metabolism through H2AZ1 deposition to activate transcription of metabolic genes, and it also maintains the stability of the respiratory complex. In neural cells, ZNHIT1 increases deposition of the H2AZ1 histone variant, promoting neurite growth. It plays a role in TP53/p53-mediated apoptosis induction by stimulating the transcriptional activation of several proapoptotic p53 target genes such as PMAIP1/NOXA and BBC3/PUMA. ZNHIT1 mediates cell cycle arrest induced in response to gamma-irradiation by enhancing recruitment of TP53/p53 to the promoter of the cell cycle inhibitor CDKN1A, leading to its transcriptional activation. It is recruited to the promoter of cyclin-dependent kinase CDK6, inhibiting its transcription, possibly by decreasing the acetylation level of histone H4, leading to cell cycle arrest at the G1 phase. ZNHIT1 plays a role in lens fiber cell differentiation by regulating the expression of the cell cycle regulator CDKN1A/p21Cip1. It binds to the transcriptional repressor NR1D2, relieving it of its inhibitory effect on the transcription of apolipoprotein APOC3 without affecting its DNA-binding activity.

ZNHIT1 is also known as CG1I, ZNFN4A1, p18(Hamlet).

Associated Diseases

WES Whole Exome Sequencing