MSL2
Description
The MSL2 (MSL complex subunit 2) is a protein-coding gene located on chromosome 3.
MSL2, also known as Male-specific lethal 2-like 1, Male-specific lethal-2 homolog, Male-specific lethal-2 homolog 1, or RING finger protein 184, is a non-catalytic component of the MSL histone acetyltransferase complex. The MSL complex is crucial for mediating the majority of histone H4 acetylation at lysine 16 (H4K16ac), an epigenetic mark preventing chromatin compaction. The MSL complex is essential for maintaining chromosome stability and genome integrity by regulating H4K16ac levels. Furthermore, it participates in gene dosage compensation by upregulating genes on the X chromosome to compensate for autosomal biallelic expression. The MSL complex also promotes expression of the Tsix non-coding RNA, contributing to gene dosage compensation. MSL2 plays a key role in ensuring biallelic expression of dosage-sensitive genes, including many haploinsufficient genes, by facilitating promoter-enhancer contacts. This prevents DNA methylation of one allele, creating a methylation-free environment for methylation-sensitive transcription factors such as SP1, KANSL1, and KANSL3. Additionally, MSL2 acts as an E3 ubiquitin ligase promoting monoubiquitination of histone H2B at lysine 35 (H2BK34Ub). This activity, enhanced by heterodimerization with MSL1, stimulates histone H3 methylation at lysine 4 (H3K4me) and lysine 79 (H3K79me), leading to gene activation. MSL2 also contributes to the DNA damage response by mediating ubiquitination of TP53/p53 and TP53BP1. MSL2 is part of a multisubunit histone acetyltransferase complex (MSL) containing KAT8/MOF/MYST1, MSL1/hampin, MSL3, and MSL2 itself. It forms a heterotetrameric core with MSL1.
MSL2 is a component of a histone acetyltransferase complex responsible for the majority of histone H4 acetylation at lysine 16, a modification implicated in chromatin structure formation. It acts as an E3 ubiquitin ligase, specifically promoting monoubiquitination of histone H2B at lysine 35 (H2BK34Ub) but not H2A. This activity is significantly enhanced when MSL2 forms a heterodimer with MSL1. H2B ubiquitination subsequently stimulates histone H3 methylation at lysine 4 (H3K4me) and lysine 79 (H3K79me), ultimately leading to gene activation, including the activation of HOXA9 and MEIS1.
MSL2 is also known as MSL-2, MSL2L1, RNF184.
